Mechanisms of Immunosuppression in Colorectal Cancer

SIMPLE SUMMARY: More emerging studies are exploring immunotherapy for solid cancers, including colorectal cancer. Besides, checkpoint blockade immunotherapy and chimeric antigen receptor (CAR) -based immune cell therapy have being examined in clinical trials for colorectal cancer patients. However, immunosuppression that leads to the blockage of normal immunosurveillance often leads to cancer development and relapse. In this study, we systematically reviewed the mechanism of immunosuppression, specifically in colorectal cancer, from different perspectives, including the natural or induced immunosuppressive cells, cell surface protein, cytokines/chemokines, transcriptional factors, metabolic alteration, phosphatase, and tissue hypoxia in the tumor microenvironment. We also discussed the progress of immunotherapies in clinical trials/studies for colorectal cancer and highlighted how different strategies for cancer therapy targeted the immunosuppression reviewed above. Our review provides some timely implications for restoring immunosurveillance to improve treatment efficacy in colorectal cancer (CRC). ABSTRACT: CRC is the third most diagnosed cancer in the US with the second-highest mortality rate. A multi-modality approach with surgery/chemotherapy is used in patients with early stages of colon cancer. Radiation therapy is added to the armamentarium in patients with locally advanced rectal cancer. While some patients with metastatic CRC are cured, the majority remain incurable and receive palliative chemotherapy as the standard of care. Recently, immune checkpoint blockade has emerged as a promising treatment for many solid tumors, including CRC with microsatellite instability. However, it has not been effective for microsatellite stable CRC. Here, main mechanisms of immunosuppression in CRC will be discussed, aiming to provide some insights for restoring immunosurveillance to improve treatment efficacy in CRC.