Selenium serves as an immunomodulator adjunct to enhance the efficacy of anti-PD-1 therapy in non-small cell lung cancer.

The role of selenium in tumor progression remains controversial, and its mechanisms of action in the context of immunotherapy are poorly understood. In this study, our findings indicate that selenium supplementation did not alter immune parameters, induce organ damage under healthy conditions, or affect the growth of Lewis lung cancer cells in vitro. In tumor-bearing mice, although selenium supplementation alone significantly enhanced the infiltration of CD8+ T cells into tumors, it failed to arrest tumor growth. Further analyses revealed that selenium treatment upregulated the expression of PD-1 on CD8+ T cells and PD-L1 on tumor cells. This finding suggests that PD-1/PD-L1 engagement may impair CD8+ T cell function, thereby preventing the effective elimination of tumor cells. Consequently, selenium supplementation exhibited a strong synergistic effect when combined with anti-PD-1 therapy, yielding enhanced antitumor responses. Single-cell RNA sequencing analysis revealed that the CD8-Prf1 subpopulation expanded and displayed enhanced proliferative and cytotoxic gene signatures after treatment with a combination of selenium and anti-PD-1. Clinically, a high abundance of this subpopulation was associated with prolonged survival in patients receiving anti-PD-1 treatment. Our results indicate that selenium is a promising immunomodulator adjunct that augments CD8+ T cell function and improves the response to anti-PD-1 therapy, supporting further clinical investigation of selenium supplementation in combination with immune checkpoint inhibitors for cancer treatment.