IL-1R2 promotes tumorigenesis and modulates the tumor immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) continues to be a major global health challenge due to its high incidence and mortality rates, emphasizing the critical need for innovative therapeutic strategies. IL-1R2, a member of the IL-1 receptor family, plays a pivotal role in both tumorigenesis and antitumor immunity. However, its precise role in tumor development and its impact on immune checkpoint inhibitors (ICIs) therapy in CRC remain poorly understood. We examined tumor progression in wild-type and IL-1R2-deficient mice using an AOM/DSS-induced colitis-associated colorectal cancer model treated with combined ICIs therapy. Our findings revealed that IL-1R2 deficient mice exhibited a significant reduction in tumor burden, accompanied by alterations in the carcinogenic program and enhanced immunogenicity of tumor cells. Furthermore, the deletion of IL-1R2 resulted in an increased proportion of exhausted CD8(+) T cells, a population commonly enriched for tumor antigen-specific T cells, suggesting an augmentation of tumor-specific immune responses. Moreover, IL-1R2 deletion upregulated genes linked to antigen presentation in dendritic cells, indicating enhanced activation of the adaptive immune system. Collectively, these findings position IL-1R2 as a promising therapeutic target for improving the efficacy of treatment strategies in CRC.