Connexin 43 Deficiency Confers Resistance to Immunotherapy in Lung Cancer via Inhibition of the Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway.

ABSTRACT: Immune checkpoint inhibitors (ICIs), especially PD-1 inhibitors, are among the first-line therapeutic drugs for the treatment of advanced non-small cell lung cancer (NSCLC). However, most patients are not sensitive to PD-1 inhibitors, and prolonged exposure can lead to acquired resistance. Thus, it is urgent to elucidate the mechanism underlying the resistance of NSCLC to ICIs. Connexin 43 (Cx43) is a gap junction (GJ) protein that is important in therapeutic efficacy to ICIs. In this study, we observed that Cx43 in murine Lewis lung carcinoma (LLC) cells mediated cyclic GMP-AMP (cGAMP) transfer to macrophages. Knockdown of Cx43 reduced T-cell activation, leading to decreased sensitivity of LLC cells to anti-PD-1 therapy. The mechanism might be that knockdown of Cx43 in LLC cells promotes

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11598135 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature