EGFR mutations induce the suppression of CD8⁺ T cell and anti-PD-1 resistance via ERK1/2-p90RSK-TGF-β axis in non-small cell lung cancer.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) patients with EGFR mutations exhibit an unfavorable response to immune checkpoint inhibitor (ICI) monotherapy, and their tumor microenvironment (TME) is usually immunosuppressed. TGF-β plays an important role in immunosuppression; however, the effects of TGF-β on the TME and the efficacy of anti-PD-1 immunotherapy against EGFR-mutated tumors remain unclear.

Methods

Corresponding in vitro studies used the TCGA database, clinical specimens, and self-constructed mouse cell lines with EGFR mutations. We utilized C57BL/6N and humanized M-NSG mouse models bearing EGFR-mutated NSCLC to investigate the effects of TGF-β on the TME and the combined efficacy of TGF-β blockade and anti-PD-1 therapy. The changes in immune cells were monitored

SUBMITTER: Huang H 

PROVIDER: S-EPMC11246587 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature