C. tropicalis promotes CRC by down-regulating tumor cell-intrinsic PD-1 receptor via autophagy.

The programmed cell death 1 (PD-1) receptor is an immune checkpoint molecule that induces immune tolerance and mediates the immune escape of tumor cells. It is mainly expressed in immune cells such as T cells, B cells and monocytes. In recent years, studies have shown that tumor cell-intrinsic PD-1 plays different roles in the development of melanoma, Liver cancer and lung cancer. However, the expression and function of PD-1 in colon cancer cells has not been reported. Our previous studies have found that () can promote CRC tumor growth and chemotherapy resistance to oxaliplatin by regulating mismatch repair system. Whether participates in the progression of CRC and immunotherapy resistance through regulating the tumor cell-intrinsic PD-1 remains to be further elucidated. In this study, we first found that high concentrations of promote tumor growth in cell cultures and xenografts. In addition, we proved that colon cancer cell lines express PD-1 receptors. Knockdown of PD-1 enhanced SW480 viability in-vitro, while overexpression of PD-1 diminished cell viability. Moreover, blocking antibody against PD-1 promotes tumor growth both in SW480 cells and mice CRC xenografts in an adaptive immune-independent manner. We also demonstrated that high concentrations of can down-regulate tumor cell-intrinsic PD-1 expression in colon cancer cells. CRC cell growth induced by is partially offset in the presence of PD-1 overexpression. This shows that promotes CRC progression via controlling the expression of tumor cell-intrinsic PD-1. Mechanistically, we found that modulates the expression of PD-1 via increasing the autophagy traffic in colon cancer cells. Combining autophagy inhibitor with treatment partly blocked the CRC tumor growth and reversed the downregulation of PD-1. This study shows that PD-1 is a tumor suppressor in CRC. can down-regulate tumor cell-intrinsic PD-1 expression via enhancing tumor cells autophagy levels to promote CRC progression. It may provide a new idea and mechanism for answering why the immune monoclonal antibody treatment is ineffective in cancer patients.