Objective To summarize the key roles of cancer-associated fibroblasts (CAFs) in the pathogenesis, development, therapeutic resistance, and immune microenvironment modulation of colorectal cancer (CRC). MethodsThrough a systematic review of existing literature, this article summarizes the origin and heterogeneity of CAFs, their mechanisms of action in CRC occurrence and progression, and reviews potential CAFs-targeting therapeutic strategies. ResultsCAFs are heterogeneous with respect to both origin and function. As a critical ingredient in tumor microenvironment, CAFs drive CRC progression by promoting tumor proliferation, invasion, metastasis, angiogenesis. CAFs can mediate therapy resistance by regulating cancer stem cell properties and suppress antitumor immunity by regulating immune checkpoint molecules. Targeting specific CAFs subsets or their key signaling pathways demonstrat tumor-suppressive effects. ConclusionsCAFs are key regulators of CRC progression. Developing targeted therapeutic strategies against their origins, heterogeneity, and functional mechanisms holds the potential to providing new directions in CRC treatment.
Objective To systematically summarize the application prospects of post-translational modifications of programmed death-1 (PD-1) in tumor immunotherapy, and provide new ideas for the immunotherapy of tumor patients. MethodsBased on the immunosuppressive mechanism of PD-1 and the clinical application status of anti PD-1 immunotherapy, combined with the existing research results on PD-1 post-translational modifications, this study systematically sorted out and analyzed the types of post-translational modifications of PD-1, their regulatory mechanisms, and their association with immunotherapy. ResultsPD-1 is an immunosuppressive molecule expressed on the surface of activated T cells, B cells and other cells. After binding to programmed death-ligand 1, it can negatively regulate the immune system. Anti PD-1/programmed death-ligand 1 immunotherapy has been widely used in the treatment of various malignant tumors, but some patients have poor response. PD-1 has various post-translational modifications such as phosphorylation, glycosylation, ubiquitination and palmitoylation, which can affect the stability and physiological functions of PD-1. ConclusionsPost-translational modifications of PD-1 are a key mechanism regulating the tumor immune evasion. Targeting the post-translational modification process of PD-1 is expected to improve the response of tumor immunotherapy and have good clinical application prospects.