The EGFR inhibitor exerts a suppressive influence on the response of CD8+ T cells in Non-Small Cell Lung Cancer

Abstract

Abstract Lung cancer is the leading cause of death worldwide, predominantly characterized by non-small cell lung cancer (NSCLC). The foremost treatment for NSCLC patients with EGFR mutations involves EGFR-tyrosine kinase inhibitors (EGFR-TKIs), demonstrating notable enhancements in patient survival and the preservation of quality of life. Immune checkpoint blockade (ICB) that reinvigorates T cell response is a promising immunotherapeutic approach to treat NSCLC patients with an efficacy of approximately 20%. Thus, comprehending the intricate interplay between EGFR-TKIs and immune regulation is pivotal, laying the groundwork for strategic combination therapies. Despite its critical importance, the relationship between EGFR-TKIs and immune regulation remains elusive, necessitating further investigation into the immunomodulatory role of EGFR-TKIs. This study unveils that EGFR-TKIs contribute to the reduced proliferation and effector cytokine production of CD8+ T cells. Treatment with EGFR-TKIs suppresses the response of tumor-infiltrating T cells in two syngeneic tumor mouse models. Furthermore, employing EGFR-TKI-specific antibodies and mass spectrum analysis, we identified the target profile of EGFR-TKIs. Remarkably, NSCLC patients undergoing EGFR-TKI therapy exhibited a diminished frequency of IFNγ-producing CD8+ T cells. These findings significantly inform the future development of therapeutic strategies and the optimization of drug administration timing for NSCLC patients.