Latest Articlesnon-coding RNA (ncRNA) is a kind of non-protein coding RNA, which plays a vital role in the initiation and development of tumor. The immune system also exhibits more complex function in tumor development. It can not only inhibit the development of tumor, but also create conditions for tumor growth. As an important means of tumor therapy, tumor immunotherapy can be regulated by non-coding RNA to achieve the goal of treatment. This article summarizes the regulation of tumor immunity by non-coding RNA.
Glioma is the most common primary intracranial tumor, among which glioblastoma (GBM) is the most malignant subtype. Because of its high heterogeneity and invasiveness, GBM can't be completely removed by surgical resection and is also resistance to chemotherapy and radiotherapy. Even after a standard therapy, the median survival time is only 14.6 months, the five-year survival rate is less than 10%, and the relapse of GBM is common. Immunotherapy, a new treatment paradigm, treats cancer through regulating the autologous immune system and the tumor microenvironment. As a promising method to improve the prognosis of GBM, immunotherapy has attracted more and more attention. This paper gives a review to the difficulty, the mainly existing strategies and the bottlenecks in GBM immunotherapy, aiming at providing new direction to improve the prognosis of GBM patients.
Immunotherapy has emerged as one of the major modalities for clinical cancer therapy, along with surgery, chemotherapy, radiotherapy and targeted therapy. However, tumor-targeted delivery of immune therapeutics is challenged by a series of barriers including non-specific release, poor tumor penetration capacity, and insufficient cellular uptake of the therapeutic regimens, which seriously restricted the efficiency and efficacy of immunotherapy. To address above challenges, nanosized drug delivery systems (NDDS) have been extensively exploited to achieve tumor-targeted delivery of immunotherapy drugs. It has been well investigated that solid tumors are of unique characteristics including acidic, hypoxic and enzymatic extracellular microenvironment. Meanwhile, the tumor cells are of acidic, reductant and reactive oxygen species intracellular microenvironment. In recent years, a large variety of tumor microenvironment-activatable NDDS have been exploited to respond specifically to the stimulus of extracellular or intracellular tumor microenvironment for enhancing the accumulation, retention and penetration in the tumor tissue. These NDDS were also employed to promote intracellular uptake and tunable drug release inside the tumor cells. In this review article, we summarized the recent progress of our laboratory using the tumor microenvironment-activatable NDDS for immune efficient therapeutics delivery, and improved cancer immunotherapy. We also briefly discussed the challenges and provided perspective of NDDS-based cancer immunotherapy.
Although numbers of naked antibodies showing clinical efficacy as single agents, their therapeutic effect is limited. Chemotherapy is very effective but with relatively large side effects, so conjugation of small chemotherapeutic drugs to antibodies is one of the important methods to enhance therapeutic potential of antibodies. Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. These modified antibodies are expected to selectively deliver chemotherapeutic drugs to tumor cells and provide sustained clinical benefit to cancer patients, at the same time, minimizing systemic toxicity. ADCs are expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand. However, designing an ADC is very complex, requiring thoughtful combination of antibody, linker, and payload drugs in the context of a target and a defined cancer indication. Although many challenges remain, recent clinical success has generated intense interest in this therapeutic class.
Distinct from conventional cancer therapies focusing directly on local tumors, cancer immunotherapy aims to restore or enhance immune surveillance to fight against cancer, which bears the advantages of less side effects, lasting efficacy, substantial specificity and suitability for individualized treatment. As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo. DCs-based immunotherapy acts by loading DCs with cancer antigens in various ways to elicit specific anti-tumor immune responses. Currently, pulsing DCs with cancer antigen encoding mRNAs is an antigen loading approach under extensive study, registering encouraging results in relevant immunotherapeutic clinical trials. Thus, pulsing DCs with mRNAs is a new and highly promising modality in cancer immunotherapy.
Carnitine palmitoyltransferase 1 (CPT1) is a fatty acid β-oxidative rate-limiting enzyme of fatty acid β-oxidation (FAO) present in the outer membrane of mitochondria, which is closely related to metabolic diseases and tumors. Numerous studies have shown that various subtypes of CPT1 are abnormally expressed in cancer cells and play an important role in resistance to metabolic stress. With the development of tumor immunotherapy, its role in immune cells and organs has also attracted attention. This article aims to review the biological functions of CPT1 and the role of different subtypes in tumor metabolism and immune regulation, and the research progress of its inhibitors, providing new ideas for cancer treatment.
In recent years, the role of ketone body metabolism in tumor growth, invasion and metastasis has attracted much attention. Succinyl-CoA transferase (SCOT) is a key enzyme in the metabolism of ketone bodies. Its function is to transfer the coenzyme A group of succinyl-CoA to acetoacetate and catalyze the formation of acetoacetyl-CoA, which is the first rate-limiting step in ketone metabolism. Then acetoacetyl-CoA further breaks into two molecules of acetyl-CoA and enters the tricarboxylic acid cycle. Studies have shown that SCOT is highly expressed in a variety of tumors, and is closely related to tumor progression and prognosis of patients, which makes SCOT a potential marker for clinical diagnosis and prognosis evaluation; in addition, inhibition of SCOT activity can hinder the metabolism of ketone bodies in tumor cells, that is, reduce the production of ATP, thereby inhibiting tumor growth, proliferation, invasion and metastasis. This review aims to explore the important role of SCOT in metabolic pathways and its relationship with tumorigenesis and development, and to provide new ideas for exploring tumor metabolism and targeting molecular drugs.
Calcium-binding protein S100A9 is closely related to inflammation and tumor invasion, and is one of the specific markers of myeloid-derived suppressor cells (MDSC). In this study, a recombinant polypeptide vaccine CTB-S100A9 targeting mouse calcium-binding protein S100A9 was constructed by fusion cholera toxin B subunit (CTB) with S100A9 gene. The CTB-S100A9 fusion protein was expressed in E coli. and purified by Ni+ affinity chromatography. Vaccinate the purified recombinant CTB-S100A9 protein supplemented with aluminum hydroxide adjuvant can break the autoimmune tolerance and produce high titer of S100A9 antibody in mice. Moreover, the S100A9 antibody produced by CTB-S100A9 vaccination is more specific and does not cross-react with S100A8. In the mouse 4T1 breast cancer model, CTB-S100A9 vaccination not only has significant tumor prevention effects, but also has significant tumor therapeutic effects. In addition, CTB-S100A9 significantly inhibited lung metastasis in 4T1 mice breast cancer model. Further analysis by flow cytometry showed that CTB-S100A9 vaccination can significantly reduce the tumor induced Treg cells and granulocyte-derived MDSC in 4T1 mice model, and reverse the tumor immunosuppressive environment, thereby promote the anti-tumor efficacy. The animal experiments in this study were carried out under the animal care guidelines approved by the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. This study shows that CTB-S100A9 is a good recombinant vaccine that targets the tumor immune-suppression environment and has great potential for the future clinical application.
Chemotherapy resistance is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Pyroptosis is one of the anti-tumor mechanisms by chemotherapy drugs. Studies have shown that DEP-domain containing mTOR-interacting protein (DEPTOR) is correlated with sorafenib and gefitnib resistance, which is discovered as a naturally negative regulator of mammalian/mechanistic target of rapamicin (mTOR). In this study, DEPTOR knockdown (shDEPTOR) lentivirus was used to establish the stable DEPTOR knockdown ESCC cell lines. The results showed that knockdown of DEPTOR reduced chemosensitivity to cisplatin in ESCC cells in vitro. The lower expression of DEPTOR caused less extensive morphological characteristics of pyroptosis than that was observed in sh-con cells with the treatment of cisplain. Further studies showed that knockdown of DEPTOR induced downregulation of Caspase-1 expression and reduction of Caspase-1 activation, thereby inhibiting the activation of the classical pathway of pyroptosis. This paper demonstrates that DEPTOR can improve cisplatin chemosensitivity in ESCC cells via inducing Caspase-1-mediated pyroptosis.
Signal transducer and activator of transcription 3 (STAT3) was found in an abnormal constitutively active status in certain cancer tissues, and under these circumstances the interruption of STAT3 signaling pathway was proposed with the potential anti-cancer efficacy. In this study, our previous reported STAT3 inhibitor Bt354 can inhibit tumor growth in DU145 xenograft mice without affecting body weight. In groups treated with Bt354, the inhibition rate of tumor weight was 58.8%, 62.7% and 73.5% in 10, 20, 40 mg·kg-1 group, respectively. Particularly, the number of Ki 67 positive cells in the tumor sections was significantly decreased in Bt354 groups. Furthermore, Bt354 inhibited the nuclear translocation of STAT3 and consequently induced cell growth inhibition, apoptosis in DU145 cells. These findings suggest that Bt354 may be a potent anticancer agent for STAT3 activated prostate cancer cells. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
