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.
Objective To systematically summarize the role of immune cells in the progression of anastomotic leak (AL) following colorectal cancer (CRC) surgery, with an emphasis on the molecular mechanisms of metabolic reprogramming in relevant immune cells, aiming to provide new insights for the diagnosis and treatment of AL. MethodWe reviewed recent literature on the metabolic reprogramming of immune cells in AL following CRC surgery. ResultsIn the postoperative CRC AL microenvironment, homeostasis imbalance drives metabolic reprogramming of immune cells (macrophages, neutrophils), manifested as enhanced glycolysis, impaired fatty acid oxidation, and tricarboxylic acid cycle disruption. Accumulated metabolites (lactate, succinate), along with acidic pH, hypoxia, and immune factors, collectively shape an intertwined immunosuppressive and pro-inflammatory microenvironment that impedes anastomotic healing. Targeting key nodes in this metabolic reprogramming offers potential therapeutic strategies and a theoretical framework for clinical translation in AL. ConclusionsImmune cells, as key components of the AL microenvironment, play an important role in the initiation and progression of AL. In-depth exploration of the molecular mechanisms underlying metabolic reprogramming of relevant immune cells may provide directions for the diagnosis and treatment of AL, with the aim of improving patients’ outcomes.