Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8⁺ T cell cytotoxicity and proliferation.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8⁺ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1

SUBMITTER: Naito Y 

PROVIDER: S-EPMC10198637 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature