The mechanistic study of novel immuno-adjuvant NCL-P2 improve the effectiveness of anti- PD-1 in colorectal cancer treatment through suppressing the expression of USP2

Objective: Colorectal cancer (CRC) has risen to second place in the incidence rate of malignant tumors in China. However, treatments for advanced CRC are not currently effective, andtreatment of anti-PD-1 monoclonal antibodies alone has no significant effect on improving the overall survival rate of CRC patients. Methods: Our research group has discovered a novel immune adjuvant NCL-P2 that can synergistically enhance the anti-CRC therapeutic effect of anti-PD-1 antibody. Results: Preliminary data shows that NCL-P2 can inhibit the expression of PD-L1 on the surface of CRC cells, activate dendritic cells, promote the secretion of cytokines such as TNFα and IL-1β , present tumor antigens, and then initiate downstream cytotoxic T cells to kill tumor cells. We found that USP2 is one of the key proteins that down regulate the expression of PD-L1 on the surface of CRC cells by NCL-P2. This project takes the CRC mouse model as the research object and explores the molecular mechanism of USP2 's impact on the expression of PD-L1 in CRC cells by activating or knocking out USP2. Conclusion: This research explores how USP2 participates in the immune activation of NCL-P2 in CRC and enhances the anti-CRC efficacy of anti-PD-1 antibody, which provides new targets and theoretical support for the clinical treatment of colorectal cancer.