Article(id=1304388107537768583, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304388047747969563, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.10.033, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1762617600000, receivedDateStr=2025-11-09, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788919959196, onlineDateStr=2026-09-09, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788919959196, onlineIssueDateStr=2026-09-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788919959196, creator=13701087609, updateTime=1788919959196, updator=13701087609, issue=Issue{id=1304388047747969563, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='10', pageStart='3685', pageEnd='4088', issueExtLink='null', onlineDate='null', pubDate='1779897600000', pubDateStr='2026-05-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788919944940, creator='13701087609', updateTime=1788923403989, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304402556332037104, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304388047747969563, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304402556332037105, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304388047747969563, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=4063, endPage=4079, ext={EN=ArticleExt(id=1304388107827175561, articleId=1304388107537768583, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Antitumor mechanism of traditional Chinese medicine regulating tumor-associated neutrophils based on “deficiency-stasis-toxin” pathogenesis, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Tumor-associated neutrophils (TANs) are immune cells with strong functional plasticity in the tumor microenvironment (TME). Their infiltration, activation, polarization balance, and formation of neutrophil extracellular traps (NETs) profoundly affect tumor occurrence, development, and immune responses. Polarization imbalance of TANs and excessive formation of NETs are key mechanisms underlying tumor immune evasion. The core pathogenesis of “deficiency-stasis-toxin” in traditional Chinese medicine (TCM) is closely related to the abnormal function of TANs: deficiency of healthy qi is the fundamental prerequisite for the abnormal function of TANs; intertwining of phlegm and stasis provides a pathological basis for the pro-tumor microenvironment of TANs; and internal accumulation of heat-toxin drives abnormal activation of TANs and amplification of inflammation. With the advantages of multi-target and multi-pathway effects, TCM regulates signaling pathways such as C-X-C motif chemokine ligand 1 (CXCL1)/C-X-C motif chemokine receptor 2 (CXCR2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) through therapeutic methods including reinforcing healthy qi and eliminating pathogens; resolving phlegm and removing stasis; clearing heat and resolving toxin. These methods can inhibit the abnormal recruitment and activation of TANs, regulate the N1/N2 polarization balance, and reduce NETs production, thereby improving the immunosuppressive state of TME and blocking tumor progression. From the perspective of integrated TCM and Western medical theories, this article systematically explains the tumor regulatory mechanism of TANs and its intrinsic correlation with the core pathogenesis of “deficiency-stasis-toxin” in TCM. It also analyzes the functional mechanism of TCM in regulating TANs based on existing research, which not only lays a theoretical foundation for revealing the scientific connotation of TCM in anti-tumor therapy but also provides core theoretical support for constructing a new integrated TCM and Western medicine strategy for TANs-targeted antitumor therapy., authors=TANG Yinggang, LIU Jie, LIN Ting, HE Yingchun, LI Dongfang, HE Lan, authorsList=TANG Yinggang, LIU Jie, LIN Ting, HE Yingchun, LI Dongfang, HE Lan, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1304388107751678088, articleId=1304388107537768583, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=基于“虚瘀毒”病机探讨中医药调控肿瘤相关中性粒细胞抗肿瘤机制, columnId=1304140194685415572, journalTitle=中草药, columnName=综述, runingTitle=null, highlight=null, articleAbstract=肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)是肿瘤微环境(tumor microenvironment,TME)中功能可塑性极强的免疫细胞,其浸润活化、极化平衡及中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)形成深刻影响肿瘤发生、发展及免疫应答。TANs极化失衡与NETs过度形成是肿瘤免疫逃逸的关键机制。中医“虚瘀毒”核心病机与TANs功能异常密切相关:正气亏虚是TANs功能异常的根本前提,痰瘀互结为TANs介导的促肿瘤微环境奠定病理基础,热毒内蕴驱动TANs异常活化及炎症放大。中医药凭借多靶点、多途径优势,通过扶正祛邪、化痰祛瘀、清热解毒等治法,靶向调控C-X-C基序趋化因子配体1(C-X-C motif chemokine ligand 1,CXCL1)/C-X-C基序趋化因子受体2(C-X-C motif chemokine receptor 2,CXCR2)、磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)、核因子-κB(nuclear factor-κB,NF-κB)、信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)等信号通路,抑制TANs异常募集与活化、调节N1/N2极化平衡、减少NETs生成,进而改善TME免疫抑制状态、阻断肿瘤进展。立足中西医理论融合视角,系统阐释TANs的肿瘤调控机制及其与中医“虚瘀毒”核心病机的内在关联,结合现有研究解析中医药调控TANs的作用逻辑,为揭示中医药抗肿瘤的科学内涵筑牢理论根基,更为构建TANs靶向治疗的中西医结合新策略提供核心理论支撑。, authors=唐迎港1, 刘洁2,3, 蔺婷2,3, 何迎春2,3, 李东芳1, 何兰4, authorsList=唐迎港, 刘洁, 蔺婷, 何迎春, 李东芳, 何兰, authorCompany=1 湖南省肿瘤医院, 湖南长沙 410013; 2 湖南省中医药防治眼耳鼻咽喉疾病与视功能保护工程技术研究中心, 湖南长沙 410208; 3 湖南中医药大学, 湖南长沙 410208; 4 湖南中医药大学第一附属医院, 湖南长沙 410007, correspAuthors=何兰, authorNote=唐迎港: 唐迎港,博士,从事中西医结合防治恶性肿瘤临床及机制研究。E-mail:tangyinggang@hnca.org.cn, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=s7xSdEWda3WytrkBSIZLQw==, pdfFileSize=953592, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=国家自然科学基金资助项目 (82305329); 国家自然科学基金资助项目 (82405496); 国家自然科学基金资助项目 (82505683); 湖南省卫生健康高层次人才重大专项 (R2023111); 湖南省自然科学基金资助项目 (2023JJ40500,2024JJ6343,2025JJ90022))}, authors=[Author(id=1307443066072228318, tenantId=1146029695717560320, journalId=null, articleId=1304388107537768583, orderNo=null, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=null, email=null, emailSecond=null, emailThird=null, correspondingAuthor=null, authorType=null, ext={EN=AuthorExt(id=null, tenantId=null, journalId=1302319053441957962, articleId=1304388107537768583, authorId=1307443066072228318, language=EN, stringName=TANG Yinggang, LIU Jie, LIN Ting, HE Yingchun, LI Dongfang, HE Lan, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=null, tenantId=null, journalId=1302319053441957962, articleId=1304388107537768583, authorId=1307443066072228318, language=CN, stringName=唐迎港, 刘洁, 蔺婷, 何迎春, 李东芳, 何兰, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=null, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=null)], keywords=[Keyword(id=1304401309575180794, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=1, keyword=虚瘀毒), Keyword(id=1304401309684232699, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=2, keyword=中医药), Keyword(id=1304401309763924476, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=3, keyword=肿瘤相关中性粒细胞), Keyword(id=1304401309852004861, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=4, keyword=肿瘤微环境), Keyword(id=1304401309948473854, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=5, keyword=中性粒细胞极化), Keyword(id=1304401310028165631, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=CN, orderNo=6, keyword=中性粒细胞胞外诱捕网), Keyword(id=1304401310258852352, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=1, keyword=deficiency-stasis-toxin), Keyword(id=1304401310393070081, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=2, keyword=traditional Chinese medicine), Keyword(id=1304401310535676418, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=3, keyword=tumor-associated neutrophils), Keyword(id=1304401310644728323, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=4, keyword=tumor microenvironment), Keyword(id=1304401310892192260, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=5, keyword=neutrophil polarization), Keyword(id=1304401311013827077, tenantId=1146029695717560320, journalId=1302319053441957962, articleId=1304388107537768583, language=EN, orderNo=6, keyword=neutrophil extracellular traps)], refs=null, funds=null, companyList=null, figs=null, attaches=null, journal=Journal(id=1302309778002903112, delFlag=0, nameCn=中草药, nameEn=Chinese Traditional and Herbal Drugs, nameHistory1=null, nameHistory2=null, issn=0253-2670, eissn=null, cn=12-1108/R, coden=null, periodic=3, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=cGpSKCP11AF8PAOcTXYWfg==, journalPrice=null, startedYear=null, abbrevIsoEn=Chinese Traditional and Herbal Drugs, journalRemark=null, publicationField=null, createdTime=1788424446827, updatedTime=1788949289390, createdBy=18614031015, updatedBy=13041195026, firstLetterCn=Z, firstLetterEn=Z, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=cGpSKCP11AF8PAOcTXYWfg==, picEn=Xw//kxUC3ON4eHxev0QLhQ==, jcr=null, cjcr=null, exts=[JournalExt(id=1304511127375863983, language=CN, name=中草药, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788949289411, updatedTime=1788949289411, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.tiprpress.com/zcy/author/login, submissionEditorUrl=https://www.tiprpress.com/zcy/editor/login, submissionReviewUrl=https://www.tiprpress.com/zcy/reviewer/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1304511127442972848, language=EN, name=Chinese Traditional and Herbal Drugs, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1788949289427, updatedTime=1788949289427, createdBy=13041195026, updatedBy=13041195026, submissionGuidelinesUrl=, submissionAuthorUrl=https://www.tiprpress.com/zcy/author/login, submissionEditorUrl=https://www.tiprpress.com/zcy/editor/login, submissionReviewUrl=https://www.tiprpress.com/zcy/reviewer/login, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1302319053441957962, websiteList=[Website(id=1302319176408912052, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1302319053441957962, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/zcy/CN, language=CN, createTime=1788426687576, createBy=18614031015, updateTime=1788427346252, updateBy=18614031015, name=中草药-中文, tplId=1146099689490845704, title=中草药, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1302322043651904087, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=articleTextType, value=kx, createTime=1788427371180, updateTime=1788427371180, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043593183828, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=banner, value=null, createTime=1788427371166, updateTime=1788427371166, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043672875610, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=grayFlag, value=0, createTime=1788427371185, updateTime=1788427371185, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043584795219, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=logo, value=https://castjournals.cast.org.cn/joweb/zcy/CN/file/pic?fileId=uiD1gpiRqR++OLOz4iKzDg==, createTime=1788427371164, updateTime=1788427371164, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043689652828, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=minRunFlag, value=0, createTime=1788427371189, updateTime=1788427371189, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043643515478, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zcy/CN/file/pic, createTime=1788427371178, updateTime=1788427371178, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043681264219, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=silenceFlag, value=0, createTime=1788427371187, updateTime=1788427371187, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043601572437, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1788427371168, updateTime=1788427371168, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043660292696, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=themeColor, value=null, createTime=1788427371182, updateTime=1788427371182, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322043668681305, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176408912052, code=themeStyle, value=null, createTime=1788427371184, updateTime=1788427371184, creator=18614031015, updator=18614031015)]), Website(id=1302319176715096246, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1302319053441957962, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/zcy/EN, language=EN, createTime=1788426687649, createBy=18614031015, updateTime=1788427341161, updateBy=18614031015, name=中草药-英文, tplId=1146101810881728533, title=Chinese Traditional and Herbal Drugs, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1302322015206134340, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=articleTextType, value=kx, createTime=1788427364398, updateTime=1788427364398, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015185162817, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=banner, value=null, createTime=1788427364393, updateTime=1788427364393, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015227105863, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=grayFlag, value=0, createTime=1788427364403, updateTime=1788427364403, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015176774208, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=logo, value=https://castjournals.cast.org.cn/joweb/zcy/EN/file/pic?fileId=uiD1gpiRqR++OLOz4iKzDg==, createTime=1788427364391, updateTime=1788427364391, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015239688777, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=minRunFlag, value=0, createTime=1788427364406, updateTime=1788427364406, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015201940035, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/zcy/EN/file/pic, createTime=1788427364397, updateTime=1788427364397, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015235494472, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=silenceFlag, value=0, createTime=1788427364405, updateTime=1788427364405, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015193551426, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1788427364395, updateTime=1788427364395, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015214522949, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=themeColor, value=null, createTime=1788427364400, updateTime=1788427364400, creator=18614031015, updator=18614031015), WebsiteProps(id=1302322015218717254, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1302319176715096246, code=themeStyle, value=null, createTime=1788427364401, updateTime=1788427364401, creator=18614031015, updator=18614031015)])], journalTitle=中草药, weixinUrl=null, journalUrl=https://www.tiprpress.com/zcy, iacademicId=null, status=1, seqNo=null, journalTitleEn=Chinese Traditional and Herbal Drugs, journalPhotoCn=cGpSKCP11AF8PAOcTXYWfg==, journalPhotoEn=Xw//kxUC3ON4eHxev0QLhQ==, journalFirstLetter=Z, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/zcy/CN/10.7501/j.issn.0253-2670.2026.10.033, detailUrlEn=https://castjournals.cast.org.cn/joweb/zcy/EN/10.7501/j.issn.0253-2670.2026.10.033, pdfUrlCn=https://castjournals.cast.org.cn/joweb/zcy/CN/PDF/10.7501/j.issn.0253-2670.2026.10.033, pdfUrlEn=https://castjournals.cast.org.cn/joweb/zcy/EN/PDF/10.7501/j.issn.0253-2670.2026.10.033, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=0, orderTime=1788919959196, fullTextJson=null, articleText=null, reference=Xu G H, Zheng J Y, Wang S, et al. Landscape of RB1 alterations in 22, 432 Chinese solid tumor patients [J]. Ann Transl Med, 2022, 10(16): 885. Davalos V, Esteller M. Cancer epigenetics in clinical practice [J]. CA A Cancer J Clin, 2023, 73(4): 376-424. Barkley D, Moncada R, Pour M, et al. Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment [J]. Nat Genet, 2022, 54(8): 1192-1201. de Visser K E, Joyce J A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth [J]. Cancer Cell, 2023, 41(3): 374-403. Liu S Y, Wu W C, Du Y S, et al. The evolution and heterogeneity of neutrophils in cancers: Origins, subsets, functions, orchestrations and clinical applications [J]. Mol Cancer, 2023, 22(1): 148. Yu T, Tang Q C, Chen X R, et al. TGF-β1 and IL-17A comediate the protumor phenotype of neutrophils to regulate the epithelial-mesenchymal transition in oral squamous cell carcinoma [J]. J Oral Pathol Med, 2021, 50(4): 353-361. Nolan E, Malanchi I. Neutrophil ‘safety net’ causes cancer cells to metastasize and proliferate [J]. Nature, 2020, 583(7814): 32-33. Adrover J M, McDowell S A C, He X Y, et al. NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps [J]. Cancer Cell, 2023, 41(3): 505-526. Köhler A, De Filippo K, Hasenberg M, et al. G-CSF–mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands [J]. Blood, 2011, 117(16): 4349-4357. Eash K J, Greenbaum A M, Gopalan P K, et al. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow [J]. J Clin Invest, 2010, 120(7): 2423-2431. Lum J J, Bren G, McClure R, et al. Elimination of senescent neutrophils by TNF-related apoptosis-inducing [corrected] ligand [J]. J Immunol, 2005, 175(2): 1232-1238. SenGupta S, Hein L E, Xu Y, et al. Triple-negative breast cancer cells recruit neutrophils by secreting TGF-β and CXCR2 ligands [J]. Front Immunol, 2021, 12: 659996. Tsumita T, Maishi N, Annan D A, et al. The oxidized-LDL/LOX-1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells [J]. Int J Cancer, 2022, 151(6): 944-956. Wang Y, Xu M H, Sun J, et al. Glycolytic neutrophils accrued in the spleen compromise anti-tumour T cell immunity in breast cancer [J]. Nat Metab, 2023, 5(8): 1408-1422. Shi T Z, Li X, Zheng J H, et al. Increased SPRY1 expression activates NF-κB signaling and promotes pancreatic cancer progression by recruiting neutrophils and macrophages through CXCL12-CXCR4 axis [J]. Cell Oncol, 2023, 46(4): 969-985. Koenderman L, Vrisekoop N. Neutrophils in cancer: From biology to therapy [J]. Cell Mol Immunol, 2025, 22(1): 4-23. Gungabeesoon J, Gort-Freitas N A, Kiss M, et al. A neutrophil response linked to tumor control in immunotherapy [J]. Cell, 2023, 186(7): 1448-1464. Zhong J H, Li Q J, Luo H Q, et al. Neutrophil-derived reactive oxygen species promote tumor colonization [J]. Commun Biol, 2021, 4: 865. Ponzetta A, Carriero R, Carnevale S, et al. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors [J]. Cell, 2019, 178(2): 346-360.e24. Chan Y T, Tan H Y, Lu Y J, et al. Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis [J]. Acta Pharm Sin B, 2023, 13(4): 1554-1567. Ali M, Fulci G, Grigalavicius M, et al. Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy [J]. Neoplasia, 2022, 26: 100779. Beauvillain C, Delneste Y, Scotet M, et al. Neutrophils efficiently cross-prime naive T cells in vivo [J]. Blood, 2007, 110(8): 2965-2973. Itatani Y, Yamamoto T, Zhong C L, et al. Suppressing neutrophil-dependent angiogenesis abrogates resistance to anti-VEGF antibody in a genetic model of colorectal cancer [J]. Proc Natl Acad Sci USA, 2020, 117(35): 21598-21608. Spiegel A, Brooks M W, Houshyar S, et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells [J]. Cancer Discov, 2016, 6(6): 630-649. Tian S B, Chu Y N, Hu J, et al. Tumour-associated neutrophils secrete AGR2 to promote colorectal cancer metastasis via its receptor CD98hc-xCT [J]. Gut, 2022, 71(12): 2489-2501. Fridlender Z G, Sun J, Kim S, et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN [J]. Cancer Cell, 2009, 16(3): 183-194. Andzinski L, Kasnitz N, Stahnke S, et al. Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human [J]. Int J Cancer, 2016, 138(8): 1982-1993. Casbon A J, Reynaud D, Park C, et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils [J]. Proc Natl Acad Sci U S A, 2015, 112(6): E566-E575. Zou J M, Qin J, Li Y C, et al. IL-35 induces N2 phenotype of neutrophils to promote tumor growth [J]. Oncotarget, 2017, 8(20): 33501-33514. Mishalian I, Bayuh R, Levy L, et al. Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression [J]. Cancer Immunol Immunother, 2013, 62(11): 1745-1756. Sagiv J Y, Michaeli J, Assi S, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer [J]. Cell Rep, 2015, 10(4): 562-573. Marini O, Costa S, Bevilacqua D, et al. Mature CD10+ and immature CD10− neutrophils present in G-CSF-treated donors display opposite effects on T cells [J]. Blood, 2017, 129(10): 1343-1356. Vadillo E, Mantilla A, Aguilar-Flores C, et al. The invasive margin of early-stage human colon tumors is infiltrated with neutrophils of an antitumoral phenotype [J]. J Leukoc Biol, 2023, 114(6): 672-683. Nie P P, Zhang W H, Meng Y, et al. A YAP/TAZ-CD54 axis is required for CXCR2–CD44– tumor-specific neutrophils to suppress gastric cancer [J]. Protein Cell, 2022: pwac045. 欧阳蒂君, 陈楠, 杨洁莹, 等. EBV阳性鼻咽癌相关性中性粒细胞抑制肿瘤微环境中的CD8+T细胞活化[J]. 中国肿瘤生物治疗杂志, 2022, 29(5): 399-409. Ohms M, Möller S, Laskay T. An attempt to polarize human neutrophils toward N1 and N2 phenotypes in vitro [J]. Front Immunol, 2020, 11: 532. Carestia A, Kaufman T, Schattner M. Platelets: New bricks in the building of neutrophil extracellular traps [J]. Front Immunol, 2016, 7: 271. Xiao Y S, Cong M, Li J T, et al. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation [J]. Cancer Cell, 2021, 39(3): 423-437.e7. Li J C, Xia Y, Sun B Y, et al. Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth [J]. Cell Commun Signal, 2023, 21(1): 86. Guimarães-Bastos D, Frony A C, Barja-Fidalgo C, et al. Melanoma-derived extracellular vesicles skew neutrophils into a pro-tumor phenotype [J]. J Leukoc Biol, 2022, 111(3): 585-596. Schoeps B, Eckfeld C, Prokopchuk O, et al. TIMP1 triggers neutrophil extracellular trap formation in pancreatic cancer[J]. Cancer Res, 2021, 81(13): 3568-3579. Alemán O R, Mora N, Cortes-Vieyra R, et al. Transforming growth factor-β-activated kinase 1 is required for human FcγRIIIb-induced neutrophil extracellular trap formation [J]. Front Immunol, 2016, 7: 277. Yang J, Jin L, Kim H S, et al. KDM6A loss recruits tumor-associated neutrophils and promotes neutrophil extracellular trap formation in pancreatic cancer [J]. Cancer Res, 2022, 82(22): 4247-4260. Holstein E, Řezníčková E, Flores T, et al. THU-478-CXCL5 induced by transforming growth factor-beta and Axl signalling causes neutrophil extracellular trap formation in hepatocellular carcinoma [J]. J Hepatol, 2019, 70(1): e371-e372. Li N, Zheng X, Chen M R, et al. Deficient DNASE1L3 facilitates neutrophil extracellular traps-induced invasion via cyclic GMP-AMP synthase and the non-canonical NF-κB pathway in diabetic hepatocellular carcinoma [J]. Clin Transl Immunol, 2022, 11(4): e1386. Li X D, Wang Z Y, Jiao C Y, et al. Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3[J]. J Transl Med, 2023, 21(1): 121. Wang Q L, Zhang Y Y, Ding W X, et al. Neutrophil extracellular traps induced by interleukin 8 via CXCR1/2 promote the progression of gastric carcinoma through transcription factor IIB-related factor 1 and cyclin [J]. Genes Dis, 2024, 11(2): 575-578. Modestino L, Cristinziano L, Trocchia M, et al. Melanoma-derived soluble mediators modulate neutrophil biological properties and the release of neutrophil extracellular traps [J]. Cancer Immunol Immunother, 2023, 72(10): 3363-3376. Weide L M, Schedel F, Weishaupt C. Neutrophil extracellular traps correlate with tumor necrosis and size in human malignant melanoma metastases [J]. Biology, 2023, 12(6): 822. Chen X J, Jiang C W, Chen M H, et al. SYK promotes the formation of neutrophil extracellular traps by inducing PKM2 nuclear translocation and promoting STAT3 phosphorylation to exacerbate hepatic ischemia-reperfusion injury and tumor recurrence [J]. Mol Med, 2024, 30(1): 146. Rosell A, Aguilera K, Hisada Y, et al. Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer [J]. Sci Rep, 2021, 11: 5074. Arelaki S, Arampatzioglou A, Kambas K, et al. Gradient infiltration of neutrophil extracellular traps in colon cancer and evidence for their involvement in tumour growth [J]. PLoS One, 2016, 11(5): e0154484. Schedel F, Mayer-Hain S, Pappelbaum K I, et al. Evidence and impact of neutrophil extracellular traps in malignant melanoma [J]. Pigment Cell Melanoma Res, 2020, 33(1): 63-73. Millrud C R, Kågedal Å, Kumlien Georén S, et al. NET-producing CD16high CD62Ldim neutrophils migrate to tumor sites and predict improved survival in patients with HNSCC [J]. Int J Cancer, 2017, 140(11): 2557-2567. 魏玉洁, 郑巧, 周宏君, 等. 基于正气亏虚思想的中医药防治肿瘤研究进展[J]. 中医药临床杂志, 2023, 35(4): 655-660. 胡锐, 孙嘉玲, 钟欣, 等. 基于RNA-Seq探讨原发性肝癌不同中医证型循环免疫细胞丰度差异[J]. 山东中医杂志, 2023, 42(9): 955-962. 张趁英, 吴兴萍, 李春华, 等. 香菇多糖对中央型非小细胞肺癌肺气亏虚型患者外周血及肺泡灌洗液IL-4、IL-12的影响[J]. 光明中医, 2020, 35(22): 3538-3541. 程锐, 张琴, 李霈瑶, 等. 益气健脾养胃煎加减辅助化疗治疗IV期胃癌及对患者预后生存的影响[J]. 陕西中医, 2025, 46(2): 215-219. 张兰鑫. 非小细胞肺癌脑转移中医证候分布特点及相关因素研究[D]. 北京: 中国中医科学院, 2023. 胡锐. 原发性肝癌免疫相关标志物筛选及气虚血瘀型循环免疫细胞微观研究[D]. 广州: 广州中医药大学, 2022. 英孝. 基于蛋白芯片技术的阴虚阳虚体质生物学基础研究[D]. 北京: 北京中医药大学, 2016. 冯磊. 阳和汤对阳虚证乳腺癌的抑制作用及相关机制的实验研究[D]. 长沙: 湖南中医药大学, 2018. 田同德, 杨峰, 岳立云, 等. 阳和汤对晚期胃癌阳虚证患者的化疗增效及其对肿瘤炎症因子, Treg, MDSCs水平的影响[J]. 中国实验方剂学杂志, 2016, 22(22): 160-164. 杜懿杰, 曹玉雪, 段晓虹, 等. 不同中医证型晚期肺腺癌患者血清、诱导痰中炎症因子与HPA轴功能的相关性研究[J]. 中国中西医结合杂志, 2012, 32(7): 896-901. 曹晨, 刘志勇, 张翔, 等. 温阳扶正方联合PD-1免疫治疗影响阳虚型肝癌微环境的临床研究[J]. 标记免疫分析与临床, 2024, 31(6): 1042-1048. Maas R R, Soukup K, Fournier N, et al. The local microenvironment drives activation of neutrophils in human brain tumors [J]. Cell, 2023, 186(21): 4546-4566.e27. Wang C X, Zheng X C, Zhang J L, et al. CD300ld on neutrophils is required for tumour-driven immune suppression [J]. Nature, 2023, 621(7980): 830-839. 于淼, 狄舒男, 周妍妍, 等. 现代医学背景下建构恶性肿瘤中医病机[J]. 世界中医药, 2022, 17(9): 1311-1315. Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis [J]. J Clin Invest, 2013, 123(8): 3446-3458. 田英洁, 吴洁, 袁国兴, 等. 基于“血小板—循环肿瘤细胞” 探讨应用肺朝百脉理论防治肿瘤转移[J]. 中国中西医结合杂志, 2025, 45(6): 735-740. 冯月男, 牛雯颖, 张玉昆, 等. 基于血小板活化和炎症相关指标探讨补阳还五汤对气虚血瘀证调控机制的研究[J]. 时珍国医国药, 2023, 34(3): 581-584. Olsson A K, Cedervall J. NETosis in cancer-platelet-neutrophil crosstalk promotes tumor-associated pathology [J]. Front Immunol, 2016, 7: 373. 张思奇, 胡凯文, 周天. 脾虚、血瘀及痰饮与乏氧肿瘤微环境研究进展[J]. 中国中医药信息杂志, 2018, 25(7): 126-129. Ugolini A, De Leo A, Yu X Q, et al. Functional reprogramming of neutrophils within the brain tumor microenvironment by hypoxia-driven histone lactylation [J]. Cancer Discov, 2025, 15(6): 1270-1296. 唐迎港, 张晓维, 何兰, 等. 基于“体寒瘤热”探析恶性肿瘤的病机与治疗[J]. 北京中医药大学学报, 2024, 47(7): 998-1004. 张传龙, 姜晓晨, 庞博, 等. 基于“热极成毒”理论探讨肺“炎-癌转化”与防治思路[J]. 北京中医药大学学报, 2022, 45(3): 291-295. 叶菁, 章杰, 许鑫雨, 等. 清热解毒药治疗恶性肿瘤研究进展[J]. 中医临床研究, 2024, 16(31): 145-148. Wang J, Xiao H H, Cui S Q, et al. The bridging role of neutrophils in the progression of inflammation-induced colorectal cancer [J]. Biochim Biophys Acta BBA Rev Cancer, 2025, 1880(6): 189460. Guglietta S, Chiavelli A, Zagato E, et al. Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis [J]. Nat Commun, 2016, 7: 11037. Wu Y C, Ma J Q, Yang X P, et al. Neutrophil profiling illuminates anti-tumor antigen-presenting potency [J]. Cell, 2024, 187(6): 1422-1439. Lian J, Lin D X, Huang Y C, et al. Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of ‘state-target identification and treatment’: A scooping review [J]. Chin Med, 2023, 18(1): 124. Keeley T, Costanzo-Garvey D L, Cook L M. Unmasking the many faces of tumor-associated neutrophils and macrophages: Considerations for targeting innate immune cells in cancer [J]. Trends Cancer, 2019, 5(12): 789-798. Yang Y, Yu S Y, Lv C, et al. NETosis in tumour microenvironment of liver: From primary to metastatic hepatic carcinoma [J]. Ageing Res Rev, 2024, 97: 102297. 夏雅雯. 人参-丹参调节转移生态位中中性粒细胞的募集与功能抑制肿瘤转移[D]. 南京: 南京中医药大学, 2022. 谢飞宇. 海花调肺方调控中性粒细胞抑制肺预转移小生境形成的机制研究[D]. 北京: 北京中医药大学, 2023. Wu X H, Xia J L, Wang Z Q, et al. Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis [J]. J Ethnopharmacol, 2022, 295: 115277. 张传龙. 中医古籍与人用经验胰腺癌用药规律挖掘及脾积丸药效机制研究[D]. 北京: 中国中医科学院, 2024. Chen L X, Li M J, Xu C Q, et al. Yi Qi Chu Tan Formula (YQCTF) inhibited the progress of lung cancer via regulating tumor-associated neutrophil: An integrated study of network pharmacology, proteomics and pharmacodynamics [J]. J Ethnopharmacol, 2024, 318: 116943. Zeng X Y, Li J X, Pei L Y, et al. Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer [J]. Pulm Circ, 2024, 14(4): e12454. 田培裕, 于泓洋, 李潇, 等. 黄芪-莪术基于C5a/NETs途径抑制Lewis肺癌小鼠肿瘤转移的机制[J]. 中国实验方剂学杂志, 2024, 30(14): 27-36. 郭春雨, 马晓娟, 刘倩, 等. 活血及活血解毒配伍中药含药血清对肿瘤坏死因子-α诱导人内皮细胞与中性粒细胞黏附及相关通路蛋白表达的影响[J]. 中国中西医结合杂志, 2015, 35(2): 204-209. Pan Z F, Xie X T, Chen Y L, et al. Huang Qin Decoction inhibits the initiation of experimental colitis associated carcinogenesis by controlling the PAD4 dependent NETs [J]. Phytomedicine, 2022, 107: 154454. Gao F, Niu Y J, Sun L Y, et al. Integrating network pharmacology and transcriptomic validation to investigate the efficacy and mechanism of Mufangji decoction preventing lung cancer [J]. J Ethnopharmacol, 2022, 298: 115573. 潘俊杰. 宋康教授治疗肺癌的用药规律探析及清肺解毒汤抗Lewis肺癌免疫调节研究[D]. 杭州: 浙江中医药大学, 2018. 谷焕鹏, 胡升芳, 凌云, 等. 解毒化浊方含药血清调控TANs对HER-2阳性乳腺癌肿瘤微环境的影响[J]. 时珍国医国药, 2023, 34(2): 299-302. 李娜. 扶正活血解毒方药对肿瘤干细胞依赖于PMNs促肿瘤转移的作用研究[D]. 北京: 中国中医科学院, 2017. Zhang Z X, Zhu Q L, Wang S Y, et al. Epigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathway [J]. Mol Cell Biochem, 2023, 478(4): 887-898. 韩君. 芦荟大黄素通过抑制中性粒细胞胞外诱捕网的形成抑制结肠癌的发展[A] // 2024中国肿瘤标志物学术大会暨CACA整合肿瘤学高峰论坛暨第十七届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会论文集[C]. 南京: 北京康仁堂药业有限公司, 2024: 25. Mou Z Z, Chen Y L, Hu J Z, et al. Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation [J]. Acta Pharm Sin B, 2024, 14(9): 3916-3930. Zhao H, Liang Y, Sun C T, et al. Dihydrotanshinone I inhibits the lung metastasis of breast cancer by suppressing neutrophil extracellular traps formation [J]. Int J Mol Sci, 2022, 23(23): 15180. Yu W Y, Wang Z N, Dai P, et al. The activation of SIRT1 by resveratrol reduces breast cancer metastasis to lung through inhibiting neutrophil extracellular traps [J]. J Drug Target, 2023, 31(9): 962-975. 崔震庭, 韩枫, 段琼, 等. 黄连素增强肺癌放射敏感性的机制研究[J]. 山西医科大学学报, 2023, 54(12): 1551-1555. 王越华. 加味麻杏石甘汤调控中性粒细胞防治肺癌的作用及机制研究[D]. 开封: 河南大学, 2021. Liu L J, Gao H J, Wen T, et al. Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation [J]. Pharm Biol, 2021, 59(1): 89-96. Ye Y Y, Xie Y, Pei L X, et al. Platycodin D induces neutrophil apoptosis by downregulating PD-L1 expression to inhibit breast cancer pulmonary metastasis [J]. Int Immunopharmacol, 2023, 115: 109733. 刘佳君, 阙祖俊, 田建辉. 金复康有效成分抑制肺癌循环肿瘤细胞募集中性粒细胞能力的比较研究[J]. 中国临床药理学与治疗学, 2023, 28(1): 1-9. Lockhart J S, Sumagin R. Non-canonical functions of myeloperoxidase in immune regulation, tissue inflammation and cancer [J]. Int J Mol Sci, 2022, 23(20): 12250. Cosic-Mujkanovic N, Valadez-Cosmes P, Maitz K, et al. Myeloperoxidase alters lung cancer cell function to benefit their survival [J]. Antioxidants, 2023, 12(8): 1587. Michaeli J, Shaul M E, Mishalian I, et al. Tumor-associated neutrophils induce apoptosis of non-activated CD8 T-cells in a TNFα and NO-dependent mechanism, promoting a tumor-supportive environment [J]. OncoImmunology, 2017, 6(11): e1356965. Wang C Y, Yang M R, Zhong Y J, et al. Immunosuppressive JAG2+ tumor-associated neutrophils hamper PD-1 blockade response in ovarian cancer by mediating the differentiation of effector regulatory T cells [J]. Cancer Commun, 2025, 45(7): 747-773. Peng Z P, Jiang Z Z, Guo H F, et al. Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma [J]. J Hepatol, 2020, 73(4): 906-917. Ashour A A, Ramadan A A, Abdelmonsif D A, et al. Enhanced oral bioavailability of Tanshinone IIA using lipid nanocapsules: Formulation, in-vitro appraisal and pharmacokinetics [J]. Int J Pharm, 2020, 586: 119598. Zhu D, Lu Y, Gui L, et al. Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment [J]. Acta Pharm Sin B, 2022, 12(5): 2592-2608. 中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版) [J]. 肿瘤防治研究, 2022, 49(3): 251-276. Reyes-Hernández O D, Figueroa-González G, Quintas-Granados L I, et al. New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives [J]. Drug Dev Res, 2024, 85(2): e22175. Mi X W, Duan Y D, Sun J Y, et al. The ketogenic diet modulates tumor-associated neutrophil polarization via the AMOT-YAP/TAZ axis to inhibit colorectal cancer progression [J]. Pharmacol Res, 2024, 210: 107494. Yazdani H O, Kaltenmeier C, Morder K, et al. Exercise training decreases hepatic injury and metastases through changes in immune response to liver ischemia/reperfusion in mice [J]. Hepatology, 2021, 73(6): 2494-2509.)
Tumor-associated neutrophils (TANs) are immune cells with strong functional plasticity in the tumor microenvironment (TME). Their infiltration, activation, polarization balance, and formation of neutrophil extracellular traps (NETs) profoundly affect tumor occurrence, development, and immune responses. Polarization imbalance of TANs and excessive formation of NETs are key mechanisms underlying tumor immune evasion. The core pathogenesis of “deficiency-stasis-toxin” in traditional Chinese medicine (TCM) is closely related to the abnormal function of TANs: deficiency of healthy qi is the fundamental prerequisite for the abnormal function of TANs; intertwining of phlegm and stasis provides a pathological basis for the pro-tumor microenvironment of TANs; and internal accumulation of heat-toxin drives abnormal activation of TANs and amplification of inflammation. With the advantages of multi-target and multi-pathway effects, TCM regulates signaling pathways such as C-X-C motif chemokine ligand 1 (CXCL1)/C-X-C motif chemokine receptor 2 (CXCR2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) through therapeutic methods including reinforcing healthy qi and eliminating pathogens; resolving phlegm and removing stasis; clearing heat and resolving toxin. These methods can inhibit the abnormal recruitment and activation of TANs, regulate the N1/N2 polarization balance, and reduce NETs production, thereby improving the immunosuppressive state of TME and blocking tumor progression. From the perspective of integrated TCM and Western medical theories, this article systematically explains the tumor regulatory mechanism of TANs and its intrinsic correlation with the core pathogenesis of “deficiency-stasis-toxin” in TCM. It also analyzes the functional mechanism of TCM in regulating TANs based on existing research, which not only lays a theoretical foundation for revealing the scientific connotation of TCM in anti-tumor therapy but also provides core theoretical support for constructing a new integrated TCM and Western medicine strategy for TANs-targeted antitumor therapy.
Key words
deficiency-stasis-toxin
/
traditional Chinese medicine
/
tumor-associated neutrophils
/
tumor microenvironment
/
neutrophil polarization
/
neutrophil extracellular traps
TANG Yinggang, LIU Jie, LIN Ting, HE Yingchun, LI Dongfang, HE Lan.
Antitumor mechanism of traditional Chinese medicine regulating tumor-associated neutrophils based on “deficiency-stasis-toxin” pathogenesis[J].
Chinese Traditional and Herbal Drugs,
2026
, 57
(10)
: 4063
-4079
.
DOI: 10.7501/j.issn.0253-2670.2026.10.033
Xu G H, Zheng J Y, Wang S, et al. Landscape of RB1 alterations in 22, 432 Chinese solid tumor patients [J]. Ann Transl Med, 2022, 10(16): 885. Davalos V, Esteller M. Cancer epigenetics in clinical practice [J]. CA A Cancer J Clin, 2023, 73(4): 376-424. Barkley D, Moncada R, Pour M, et al. Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment [J]. Nat Genet, 2022, 54(8): 1192-1201. de Visser K E, Joyce J A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth [J]. Cancer Cell, 2023, 41(3): 374-403. Liu S Y, Wu W C, Du Y S, et al. The evolution and heterogeneity of neutrophils in cancers: Origins, subsets, functions, orchestrations and clinical applications [J]. Mol Cancer, 2023, 22(1): 148. Yu T, Tang Q C, Chen X R, et al. TGF-β1 and IL-17A comediate the protumor phenotype of neutrophils to regulate the epithelial-mesenchymal transition in oral squamous cell carcinoma [J]. J Oral Pathol Med, 2021, 50(4): 353-361. Nolan E, Malanchi I. Neutrophil ‘safety net’ causes cancer cells to metastasize and proliferate [J]. Nature, 2020, 583(7814): 32-33. Adrover J M, McDowell S A C, He X Y, et al. NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps [J]. Cancer Cell, 2023, 41(3): 505-526. Köhler A, De Filippo K, Hasenberg M, et al. G-CSF–mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands [J]. Blood, 2011, 117(16): 4349-4357. Eash K J, Greenbaum A M, Gopalan P K, et al. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow [J]. J Clin Invest, 2010, 120(7): 2423-2431. Lum J J, Bren G, McClure R, et al. Elimination of senescent neutrophils by TNF-related apoptosis-inducing [corrected] ligand [J]. J Immunol, 2005, 175(2): 1232-1238. SenGupta S, Hein L E, Xu Y, et al. Triple-negative breast cancer cells recruit neutrophils by secreting TGF-β and CXCR2 ligands [J]. Front Immunol, 2021, 12: 659996. Tsumita T, Maishi N, Annan D A, et al. The oxidized-LDL/LOX-1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells [J]. Int J Cancer, 2022, 151(6): 944-956. Wang Y, Xu M H, Sun J, et al. Glycolytic neutrophils accrued in the spleen compromise anti-tumour T cell immunity in breast cancer [J]. Nat Metab, 2023, 5(8): 1408-1422. Shi T Z, Li X, Zheng J H, et al. Increased SPRY1 expression activates NF-κB signaling and promotes pancreatic cancer progression by recruiting neutrophils and macrophages through CXCL12-CXCR4 axis [J]. Cell Oncol, 2023, 46(4): 969-985. Koenderman L, Vrisekoop N. Neutrophils in cancer: From biology to therapy [J]. Cell Mol Immunol, 2025, 22(1): 4-23. Gungabeesoon J, Gort-Freitas N A, Kiss M, et al. A neutrophil response linked to tumor control in immunotherapy [J]. Cell, 2023, 186(7): 1448-1464. Zhong J H, Li Q J, Luo H Q, et al. Neutrophil-derived reactive oxygen species promote tumor colonization [J]. Commun Biol, 2021, 4: 865. Ponzetta A, Carriero R, Carnevale S, et al. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors [J]. Cell, 2019, 178(2): 346-360.e24. Chan Y T, Tan H Y, Lu Y J, et al. Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis [J]. Acta Pharm Sin B, 2023, 13(4): 1554-1567. Ali M, Fulci G, Grigalavicius M, et al. Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy [J]. Neoplasia, 2022, 26: 100779. Beauvillain C, Delneste Y, Scotet M, et al. Neutrophils efficiently cross-prime naive T cells in vivo [J]. Blood, 2007, 110(8): 2965-2973. Itatani Y, Yamamoto T, Zhong C L, et al. Suppressing neutrophil-dependent angiogenesis abrogates resistance to anti-VEGF antibody in a genetic model of colorectal cancer [J]. Proc Natl Acad Sci USA, 2020, 117(35): 21598-21608. Spiegel A, Brooks M W, Houshyar S, et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells [J]. Cancer Discov, 2016, 6(6): 630-649. Tian S B, Chu Y N, Hu J, et al. Tumour-associated neutrophils secrete AGR2 to promote colorectal cancer metastasis via its receptor CD98hc-xCT [J]. Gut, 2022, 71(12): 2489-2501. Fridlender Z G, Sun J, Kim S, et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN [J]. Cancer Cell, 2009, 16(3): 183-194. Andzinski L, Kasnitz N, Stahnke S, et al. Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human [J]. Int J Cancer, 2016, 138(8): 1982-1993. Casbon A J, Reynaud D, Park C, et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils [J]. Proc Natl Acad Sci U S A, 2015, 112(6): E566-E575. Zou J M, Qin J, Li Y C, et al. IL-35 induces N2 phenotype of neutrophils to promote tumor growth [J]. Oncotarget, 2017, 8(20): 33501-33514. Mishalian I, Bayuh R, Levy L, et al. Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during tumor progression [J]. Cancer Immunol Immunother, 2013, 62(11): 1745-1756. Sagiv J Y, Michaeli J, Assi S, et al. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer [J]. Cell Rep, 2015, 10(4): 562-573. Marini O, Costa S, Bevilacqua D, et al. Mature CD10+ and immature CD10− neutrophils present in G-CSF-treated donors display opposite effects on T cells [J]. Blood, 2017, 129(10): 1343-1356. Vadillo E, Mantilla A, Aguilar-Flores C, et al. The invasive margin of early-stage human colon tumors is infiltrated with neutrophils of an antitumoral phenotype [J]. J Leukoc Biol, 2023, 114(6): 672-683. Nie P P, Zhang W H, Meng Y, et al. A YAP/TAZ-CD54 axis is required for CXCR2–CD44– tumor-specific neutrophils to suppress gastric cancer [J]. Protein Cell, 2022: pwac045. 欧阳蒂君, 陈楠, 杨洁莹, 等. EBV阳性鼻咽癌相关性中性粒细胞抑制肿瘤微环境中的CD8+T细胞活化[J]. 中国肿瘤生物治疗杂志, 2022, 29(5): 399-409. Ohms M, Möller S, Laskay T. An attempt to polarize human neutrophils toward N1 and N2 phenotypes in vitro [J]. Front Immunol, 2020, 11: 532. Carestia A, Kaufman T, Schattner M. Platelets: New bricks in the building of neutrophil extracellular traps [J]. Front Immunol, 2016, 7: 271. Xiao Y S, Cong M, Li J T, et al. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation [J]. Cancer Cell, 2021, 39(3): 423-437.e7. Li J C, Xia Y, Sun B Y, et al. Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth [J]. Cell Commun Signal, 2023, 21(1): 86. Guimarães-Bastos D, Frony A C, Barja-Fidalgo C, et al. Melanoma-derived extracellular vesicles skew neutrophils into a pro-tumor phenotype [J]. J Leukoc Biol, 2022, 111(3): 585-596. Schoeps B, Eckfeld C, Prokopchuk O, et al. TIMP1 triggers neutrophil extracellular trap formation in pancreatic cancer[J]. Cancer Res, 2021, 81(13): 3568-3579. Alemán O R, Mora N, Cortes-Vieyra R, et al. Transforming growth factor-β-activated kinase 1 is required for human FcγRIIIb-induced neutrophil extracellular trap formation [J]. Front Immunol, 2016, 7: 277. Yang J, Jin L, Kim H S, et al. KDM6A loss recruits tumor-associated neutrophils and promotes neutrophil extracellular trap formation in pancreatic cancer [J]. Cancer Res, 2022, 82(22): 4247-4260. Holstein E, Řezníčková E, Flores T, et al. THU-478-CXCL5 induced by transforming growth factor-beta and Axl signalling causes neutrophil extracellular trap formation in hepatocellular carcinoma [J]. J Hepatol, 2019, 70(1): e371-e372. Li N, Zheng X, Chen M R, et al. Deficient DNASE1L3 facilitates neutrophil extracellular traps-induced invasion via cyclic GMP-AMP synthase and the non-canonical NF-κB pathway in diabetic hepatocellular carcinoma [J]. Clin Transl Immunol, 2022, 11(4): e1386. Li X D, Wang Z Y, Jiao C Y, et al. Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3[J]. J Transl Med, 2023, 21(1): 121. Wang Q L, Zhang Y Y, Ding W X, et al. Neutrophil extracellular traps induced by interleukin 8 via CXCR1/2 promote the progression of gastric carcinoma through transcription factor IIB-related factor 1 and cyclin [J]. Genes Dis, 2024, 11(2): 575-578. Modestino L, Cristinziano L, Trocchia M, et al. Melanoma-derived soluble mediators modulate neutrophil biological properties and the release of neutrophil extracellular traps [J]. Cancer Immunol Immunother, 2023, 72(10): 3363-3376. Weide L M, Schedel F, Weishaupt C. Neutrophil extracellular traps correlate with tumor necrosis and size in human malignant melanoma metastases [J]. Biology, 2023, 12(6): 822. Chen X J, Jiang C W, Chen M H, et al. SYK promotes the formation of neutrophil extracellular traps by inducing PKM2 nuclear translocation and promoting STAT3 phosphorylation to exacerbate hepatic ischemia-reperfusion injury and tumor recurrence [J]. Mol Med, 2024, 30(1): 146. Rosell A, Aguilera K, Hisada Y, et al. Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer [J]. Sci Rep, 2021, 11: 5074. Arelaki S, Arampatzioglou A, Kambas K, et al. Gradient infiltration of neutrophil extracellular traps in colon cancer and evidence for their involvement in tumour growth [J]. PLoS One, 2016, 11(5): e0154484. Schedel F, Mayer-Hain S, Pappelbaum K I, et al. Evidence and impact of neutrophil extracellular traps in malignant melanoma [J]. Pigment Cell Melanoma Res, 2020, 33(1): 63-73. Millrud C R, Kågedal Å, Kumlien Georén S, et al. NET-producing CD16high CD62Ldim neutrophils migrate to tumor sites and predict improved survival in patients with HNSCC [J]. Int J Cancer, 2017, 140(11): 2557-2567. 魏玉洁, 郑巧, 周宏君, 等. 基于正气亏虚思想的中医药防治肿瘤研究进展[J]. 中医药临床杂志, 2023, 35(4): 655-660. 胡锐, 孙嘉玲, 钟欣, 等. 基于RNA-Seq探讨原发性肝癌不同中医证型循环免疫细胞丰度差异[J]. 山东中医杂志, 2023, 42(9): 955-962. 张趁英, 吴兴萍, 李春华, 等. 香菇多糖对中央型非小细胞肺癌肺气亏虚型患者外周血及肺泡灌洗液IL-4、IL-12的影响[J]. 光明中医, 2020, 35(22): 3538-3541. 程锐, 张琴, 李霈瑶, 等. 益气健脾养胃煎加减辅助化疗治疗IV期胃癌及对患者预后生存的影响[J]. 陕西中医, 2025, 46(2): 215-219. 张兰鑫. 非小细胞肺癌脑转移中医证候分布特点及相关因素研究[D]. 北京: 中国中医科学院, 2023. 胡锐. 原发性肝癌免疫相关标志物筛选及气虚血瘀型循环免疫细胞微观研究[D]. 广州: 广州中医药大学, 2022. 英孝. 基于蛋白芯片技术的阴虚阳虚体质生物学基础研究[D]. 北京: 北京中医药大学, 2016. 冯磊. 阳和汤对阳虚证乳腺癌的抑制作用及相关机制的实验研究[D]. 长沙: 湖南中医药大学, 2018. 田同德, 杨峰, 岳立云, 等. 阳和汤对晚期胃癌阳虚证患者的化疗增效及其对肿瘤炎症因子, Treg, MDSCs水平的影响[J]. 中国实验方剂学杂志, 2016, 22(22): 160-164. 杜懿杰, 曹玉雪, 段晓虹, 等. 不同中医证型晚期肺腺癌患者血清、诱导痰中炎症因子与HPA轴功能的相关性研究[J]. 中国中西医结合杂志, 2012, 32(7): 896-901. 曹晨, 刘志勇, 张翔, 等. 温阳扶正方联合PD-1免疫治疗影响阳虚型肝癌微环境的临床研究[J]. 标记免疫分析与临床, 2024, 31(6): 1042-1048. Maas R R, Soukup K, Fournier N, et al. The local microenvironment drives activation of neutrophils in human brain tumors [J]. Cell, 2023, 186(21): 4546-4566.e27. Wang C X, Zheng X C, Zhang J L, et al. CD300ld on neutrophils is required for tumour-driven immune suppression [J]. Nature, 2023, 621(7980): 830-839. 于淼, 狄舒男, 周妍妍, 等. 现代医学背景下建构恶性肿瘤中医病机[J]. 世界中医药, 2022, 17(9): 1311-1315. Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis [J]. J Clin Invest, 2013, 123(8): 3446-3458. 田英洁, 吴洁, 袁国兴, 等. 基于“血小板—循环肿瘤细胞” 探讨应用肺朝百脉理论防治肿瘤转移[J]. 中国中西医结合杂志, 2025, 45(6): 735-740. 冯月男, 牛雯颖, 张玉昆, 等. 基于血小板活化和炎症相关指标探讨补阳还五汤对气虚血瘀证调控机制的研究[J]. 时珍国医国药, 2023, 34(3): 581-584. Olsson A K, Cedervall J. NETosis in cancer-platelet-neutrophil crosstalk promotes tumor-associated pathology [J]. Front Immunol, 2016, 7: 373. 张思奇, 胡凯文, 周天. 脾虚、血瘀及痰饮与乏氧肿瘤微环境研究进展[J]. 中国中医药信息杂志, 2018, 25(7): 126-129. Ugolini A, De Leo A, Yu X Q, et al. Functional reprogramming of neutrophils within the brain tumor microenvironment by hypoxia-driven histone lactylation [J]. Cancer Discov, 2025, 15(6): 1270-1296. 唐迎港, 张晓维, 何兰, 等. 基于“体寒瘤热”探析恶性肿瘤的病机与治疗[J]. 北京中医药大学学报, 2024, 47(7): 998-1004. 张传龙, 姜晓晨, 庞博, 等. 基于“热极成毒”理论探讨肺“炎-癌转化”与防治思路[J]. 北京中医药大学学报, 2022, 45(3): 291-295. 叶菁, 章杰, 许鑫雨, 等. 清热解毒药治疗恶性肿瘤研究进展[J]. 中医临床研究, 2024, 16(31): 145-148. Wang J, Xiao H H, Cui S Q, et al. The bridging role of neutrophils in the progression of inflammation-induced colorectal cancer [J]. Biochim Biophys Acta BBA Rev Cancer, 2025, 1880(6): 189460. Guglietta S, Chiavelli A, Zagato E, et al. Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis [J]. Nat Commun, 2016, 7: 11037. Wu Y C, Ma J Q, Yang X P, et al. Neutrophil profiling illuminates anti-tumor antigen-presenting potency [J]. Cell, 2024, 187(6): 1422-1439. Lian J, Lin D X, Huang Y C, et al. Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of ‘state-target identification and treatment’: A scooping review [J]. Chin Med, 2023, 18(1): 124. Keeley T, Costanzo-Garvey D L, Cook L M. Unmasking the many faces of tumor-associated neutrophils and macrophages: Considerations for targeting innate immune cells in cancer [J]. Trends Cancer, 2019, 5(12): 789-798. Yang Y, Yu S Y, Lv C, et al. NETosis in tumour microenvironment of liver: From primary to metastatic hepatic carcinoma [J]. Ageing Res Rev, 2024, 97: 102297. 夏雅雯. 人参-丹参调节转移生态位中中性粒细胞的募集与功能抑制肿瘤转移[D]. 南京: 南京中医药大学, 2022. 谢飞宇. 海花调肺方调控中性粒细胞抑制肺预转移小生境形成的机制研究[D]. 北京: 北京中医药大学, 2023. Wu X H, Xia J L, Wang Z Q, et al. Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis [J]. J Ethnopharmacol, 2022, 295: 115277. 张传龙. 中医古籍与人用经验胰腺癌用药规律挖掘及脾积丸药效机制研究[D]. 北京: 中国中医科学院, 2024. Chen L X, Li M J, Xu C Q, et al. Yi Qi Chu Tan Formula (YQCTF) inhibited the progress of lung cancer via regulating tumor-associated neutrophil: An integrated study of network pharmacology, proteomics and pharmacodynamics [J]. J Ethnopharmacol, 2024, 318: 116943. Zeng X Y, Li J X, Pei L Y, et al. Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer [J]. Pulm Circ, 2024, 14(4): e12454. 田培裕, 于泓洋, 李潇, 等. 黄芪-莪术基于C5a/NETs途径抑制Lewis肺癌小鼠肿瘤转移的机制[J]. 中国实验方剂学杂志, 2024, 30(14): 27-36. 郭春雨, 马晓娟, 刘倩, 等. 活血及活血解毒配伍中药含药血清对肿瘤坏死因子-α诱导人内皮细胞与中性粒细胞黏附及相关通路蛋白表达的影响[J]. 中国中西医结合杂志, 2015, 35(2): 204-209. Pan Z F, Xie X T, Chen Y L, et al. Huang Qin Decoction inhibits the initiation of experimental colitis associated carcinogenesis by controlling the PAD4 dependent NETs [J]. Phytomedicine, 2022, 107: 154454. Gao F, Niu Y J, Sun L Y, et al. Integrating network pharmacology and transcriptomic validation to investigate the efficacy and mechanism of Mufangji decoction preventing lung cancer [J]. J Ethnopharmacol, 2022, 298: 115573. 潘俊杰. 宋康教授治疗肺癌的用药规律探析及清肺解毒汤抗Lewis肺癌免疫调节研究[D]. 杭州: 浙江中医药大学, 2018. 谷焕鹏, 胡升芳, 凌云, 等. 解毒化浊方含药血清调控TANs对HER-2阳性乳腺癌肿瘤微环境的影响[J]. 时珍国医国药, 2023, 34(2): 299-302. 李娜. 扶正活血解毒方药对肿瘤干细胞依赖于PMNs促肿瘤转移的作用研究[D]. 北京: 中国中医科学院, 2017. Zhang Z X, Zhu Q L, Wang S Y, et al. Epigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathway [J]. Mol Cell Biochem, 2023, 478(4): 887-898. 韩君. 芦荟大黄素通过抑制中性粒细胞胞外诱捕网的形成抑制结肠癌的发展[A] // 2024中国肿瘤标志物学术大会暨CACA整合肿瘤学高峰论坛暨第十七届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会论文集[C]. 南京: 北京康仁堂药业有限公司, 2024: 25. Mou Z Z, Chen Y L, Hu J Z, et al. Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation [J]. Acta Pharm Sin B, 2024, 14(9): 3916-3930. Zhao H, Liang Y, Sun C T, et al. Dihydrotanshinone I inhibits the lung metastasis of breast cancer by suppressing neutrophil extracellular traps formation [J]. Int J Mol Sci, 2022, 23(23): 15180. Yu W Y, Wang Z N, Dai P, et al. The activation of SIRT1 by resveratrol reduces breast cancer metastasis to lung through inhibiting neutrophil extracellular traps [J]. J Drug Target, 2023, 31(9): 962-975. 崔震庭, 韩枫, 段琼, 等. 黄连素增强肺癌放射敏感性的机制研究[J]. 山西医科大学学报, 2023, 54(12): 1551-1555. 王越华. 加味麻杏石甘汤调控中性粒细胞防治肺癌的作用及机制研究[D]. 开封: 河南大学, 2021. Liu L J, Gao H J, Wen T, et al. Tanshinone IIA attenuates AOM/DSS-induced colorectal tumorigenesis in mice via inhibition of intestinal inflammation [J]. Pharm Biol, 2021, 59(1): 89-96. Ye Y Y, Xie Y, Pei L X, et al. Platycodin D induces neutrophil apoptosis by downregulating PD-L1 expression to inhibit breast cancer pulmonary metastasis [J]. Int Immunopharmacol, 2023, 115: 109733. 刘佳君, 阙祖俊, 田建辉. 金复康有效成分抑制肺癌循环肿瘤细胞募集中性粒细胞能力的比较研究[J]. 中国临床药理学与治疗学, 2023, 28(1): 1-9. Lockhart J S, Sumagin R. Non-canonical functions of myeloperoxidase in immune regulation, tissue inflammation and cancer [J]. Int J Mol Sci, 2022, 23(20): 12250. Cosic-Mujkanovic N, Valadez-Cosmes P, Maitz K, et al. Myeloperoxidase alters lung cancer cell function to benefit their survival [J]. Antioxidants, 2023, 12(8): 1587. Michaeli J, Shaul M E, Mishalian I, et al. Tumor-associated neutrophils induce apoptosis of non-activated CD8 T-cells in a TNFα and NO-dependent mechanism, promoting a tumor-supportive environment [J]. OncoImmunology, 2017, 6(11): e1356965. Wang C Y, Yang M R, Zhong Y J, et al. Immunosuppressive JAG2+ tumor-associated neutrophils hamper PD-1 blockade response in ovarian cancer by mediating the differentiation of effector regulatory T cells [J]. Cancer Commun, 2025, 45(7): 747-773. Peng Z P, Jiang Z Z, Guo H F, et al. Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma [J]. J Hepatol, 2020, 73(4): 906-917. Ashour A A, Ramadan A A, Abdelmonsif D A, et al. Enhanced oral bioavailability of Tanshinone IIA using lipid nanocapsules: Formulation, in-vitro appraisal and pharmacokinetics [J]. Int J Pharm, 2020, 586: 119598. Zhu D, Lu Y, Gui L, et al. Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment [J]. Acta Pharm Sin B, 2022, 12(5): 2592-2608. 中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版) [J]. 肿瘤防治研究, 2022, 49(3): 251-276. Reyes-Hernández O D, Figueroa-González G, Quintas-Granados L I, et al. New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives [J]. Drug Dev Res, 2024, 85(2): e22175. Mi X W, Duan Y D, Sun J Y, et al. The ketogenic diet modulates tumor-associated neutrophil polarization via the AMOT-YAP/TAZ axis to inhibit colorectal cancer progression [J]. Pharmacol Res, 2024, 210: 107494. Yazdani H O, Kaltenmeier C, Morder K, et al. Exercise training decreases hepatic injury and metastases through changes in immune response to liver ischemia/reperfusion in mice [J]. Hepatology, 2021, 73(6): 2494-2509.