Latest ArticlesThe research aims to study the effects of different stimulants on the activation of human lymphocytes. Human peripheral blood mononuclear cells were prepared by density centrifugation. The blood's sample was provided by National Institutes for Food and Drug Control and approved by its Ethics Committee. The expressions of CD69 in CD3+CD4+ and CD3+CD8+ human T cells were detected by flow cytometry after administrated with CD3/CD28 antibody, phytohaemagglutinin (PHA), Staphylococcus auresus enterooxin B (SEB), interleukin (IL27) and PMA plus ionomycin for 24 h. The proliferation of lymphocyte was detected by CellTiter-Glo kit. The secreted IFNγ in supernatant of medium was examined by ELISA kit. The proliferation of lymphocytes had no change after exposed of CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin for 24 h. However, the CD69 expressions in CD3+CD4+ and CD3+CD8+ T cells and IFNγ productions were significantly increased by CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin at 24 h, indicating that CD3+CD4+ and CD3+CD8+ T cells were activated under above-mentioned stimulated condition. CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin were valid stimulants for T cell activation.
Tumor immunotherapy is a critical field in the development of anticancer drugs. The research of stimulator of interferon genes (STING) agonist provides a new idea for immunotherapy. Innate immune response can effectively be induced by nucleic acids in mammalian cytoplasm. In recent years, a large number of studies have confirmed that the cGAS-cGAMP-STING signaling pathway plays a key role in cytoplasmic DNA recognition and immune defense activation. The dysfunction of cGAS-cGAMP-STING is closely related to the tumorigenesis, and is a potent target for drug development. In this study, based on THP-1 dual cells which are stably expressing cGAS-STING pathway and THP-1 KO-STING cells which are stably depleted STING, a screening method for STING agonists was established by detection of luciferase. Furthermore, the accuracy and sensitivity of the model were verified using positive compound, providing a simple, efficient and accurate screening platform for high-throughput screening of STING agonists.
We explore and verify the optimized condition for HEK-Blue IL-17 screening model, and screen the compounds that inhibits IL-17-medited signaling pathway. HEK-Blue IL-17 cells (5×104 cells per well) were seeded into the 96 plates followed by different concentrations of IL-17A or IL-17F alone, or in combination with tested compounds for 16 h. Then, the supernatant medium was incubated with QUANTI-Blue for 1 or 3 h to detect the OD value at λ655 nm. The secreted alkaline phosphatase (SEAP) production was an index of IL-17-mediated signaling activation in HEK-Blue IL-17 cells. We found that both IL-17A and IL-17F can significantly activate the IL-17 signaling pathway in HEK-Blue IL-17 cells. The available dosage of IL-17A and IL-17F were 10 and 100 ng·mL-1, respectively. The reaction time of SEAP and QUANTI-Blue was 1 h. In this model, arctigenin and epigallocatechin gallate (EGCG) could inhibit the IL-17A and IL-17F-mediated signaling pathway. This established and optimized screening model of HEK-Blue IL-17 cells was suitable for screening inhibitors of IL-17-mediated signaling pathway.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, which is charac-terized by complex pathogenesis, inconspicuous early symptoms, rapid progress and poor prognosis. Immuno-therapy and targeted therapy are important methods to treat advanced and metastatic liver cancer in recent years. With the FDA's approval of sorafenib and other tyrosine kinase inhibitors and programmed cell death protein 1 and cytotoxic T lymphocyte-associated antigen-4 immune checkpoint inhibitors for the treatment of liver cancer, great progress has been made in single-agent therapy and combination therapy, bringing a new turning point for the improvement of survival rate of patients with advanced liver cancer. However, the mechanism of immunotherapy and drug resistance is still unclear, and its clinical application combined with targeted and other therapies is still under research, which needs to be further explored by researchers. In this paper, the clinical research progress of immunotherapy combined with other therapies in advanced hepatocellular carcinoma was reviewed, in order to grasp the current development trend of the treatment of hepatocellular carcinoma and provide reference for the further development direction of immunotherapy.
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.
Chemotherapeutic agents, also known as cytotoxic anticancer agents, inhibit the cancer cell proliferation via interrupting DNA replication, transcription and microtubule stability etc. Chemotherapeutic agents have been used in clinical cancer treatment for decades. Recently, with the tremendous advancement in immunooncology, chemotherapeutic agents have aroused renewed interest for their great potential to sensitize tumor cells to immunotherapy. Meanwhile, it is worth noting that the effects of chemotherapeutic agents on the immune system involve multiple aspects with complex mechanisms. Currently, there still lacks guidance for the combined use of chemotherapy and immunotherapy, and the clinical benefits remain obscure, impelling a better under-standing of the impact of chemotherapeutic agents on the antitumor immunity. This article reviews the mechanistic insights into chemotherapy-modulated antitumor immune responses, with major focus on the direct effect on immune cells and the immunogenic remodeling of tumor cells. The review is particularly interested in the chemo-therapy-trigged signaling that contributes to the immunogenic cell death. This review may provide useful insights into the immunomodulatory effects of chemotherapeutic agents and the implications in exploring therapeutic oppor-tunities of chemotherapy in cancer immunotherapy.
N6-methyladenosine (m6A) modification is one of the most common modifications of eukaryotic mRNA, and has become a hotspot in the field of life sciences in recent years. m6A modification is dynamically reversible in mammalian cells and regulated by m6A methyltransferase (writers), demethylase (erasers), and "reader" proteins. m6A can regulate various biological processes of mRNA such as RNA splicing, nuclear export, protein translation and degradation. Recent studies indicated that m6A is important for the initiation and development of cancer. The present review summarized biological functions of m6A on mRNA and discussed its roles in cell proliferation, migration, invasion, cell mentalism, and angiogenesis. Further, the m6A can regulate the development of various cancers including acute myelocytic leukemia (AML), breast, liver and colorectal cancer. Nowadays, the inhibitors of m6A related enzymes including fat-mass and obesity-associated protein and AlkB homolog 5 are being developed. We further discussed the potential values of m6A and its related targets on cancer therapy and treatment.
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.
non-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.
Metabolic remodeling, a well-recognized hallmark of cancer, provides biomass and energy to support the growing demand of unrestricted growth of cancer cells. In addition to metabolic supplies, the altered cell metabolism often results in the intracellular accumulation of particular metabolites. Recently, it is increasingly revealed these metabolites may exhibit metabolism-independent roles as signaling molecules, which triggers oncogenic signaling via various mechanisms including competitive inhibition, protein post-translational modifica-tions and direct protein binding. These insights provide a new perspective of metabolic remodeling in cancer progression. This review summarized the recent advancement in the understanding of metabolites as signaling molecules independent rewriting of metabolic pathways. By summarizing these progresses, this review hopes to provide a better understanding of tumor metabolic disturbance and to contribute to the discovery of novel potential therapeutic targets.
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