Castration-Resistant Prostate Cancer (CRPC) exhibits complex immune evasion mechanisms, such as inhibiting immune cell activity and selectively expressing low-immunogenic antigens, which allow the cancer to escape immune system recognition. These mechanisms contribute to poor responses to immunotherapy. As a result, new combination treatment strategies are needed to improve immunotherapy effectiveness. Sesamin, a natural compound extracted from sesame seeds, has been shown to enhance immune responses, suggesting its potential application in immunotherapy and cancer prevention.

The objective of this study is to investigate the mechanism by which sesamin enhances the tumor immune microenvironment by inhibiting the expression of soluble PD-L1. This could provide new strategies for the clinical immunotherapy of prostate cancer. Western blotting and real-time RT-PCR will be used to analyze protein expression and mRNA levels. Enzyme-Linked Immunosorbent Assay (ELISA) will be employed to measure the expression of soluble PD-L1. Co-immunoprecipitation (Co-IP) will confirm protein-protein interactions, and flow cytometry will be used to assess the apoptosis of natural killer (NK) cells.

The study will analyze the inhibitory effect of sesamin on the release of soluble PD-L1 by prostate cancer cells. It will demonstrate that sesamin inhibits the activity of ADAM9, which is responsible for cleaving PD-L1. Using an in vitro experimental model, it will be shown that sesamin enhances the prostate tumor immune microenvironment by inhibiting the ADAM9/PD-L1 pathway.

This study demonstrates that sesamin inhibits ADAM9-mediated PD-L1 cleavage, thereby enhancing the tumor immune microenvironment in prostate cancer. These findings suggest that sesamin could be a promising adjunct in immunotherapy by targeting the ADAM9/PD-L1 axis.