KRAS-G12D mutation drives immune suppression and the primary resistance of anti-PD-1/PD-L1 immunotherapy in non-small cell lung cancer.

ABSTRACT:

Background

Although immune checkpoint inhibitors (ICIs) against programmed cell death protein 1 (PD-1) and its ligand PD-L1 have demonstrated potency towards treating patients with non-small cell lung carcinoma (NSCLC), the potential association between Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene substitutions and the efficacy of ICIs remains unclear. In this study, we aimed to find point mutations in the KRAS gene resistant to ICIs and elucidate resistance mechanism.

Methods

The association between KRAS variant status and the efficacy of ICIs was explored with a clinical cohort (n = 74), and confirmed with a mouse model. In addition, the tumor immune microenvironment (TIME) of KRAS-mutant NSCLC, such as CD8⁺ tumor-infiltrating lymphocytes (TILs) an

SUBMITTER: Liu C 

PROVIDER: S-EPMC9456691 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature