Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

ABSTRACT: LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited. Here, we report that loss of LKB1 results in increased secretion of the C-X-C motif (CXC) chemokines with an NH2-terminal Glu-Leu-Arg (ELR) motif in premalignant and cancerous cells, as well as in genetically engineered murine models (GEMM) of NSCLC. Heightened levels of ELR⁺ CXC chemokines in LKB1-deficient murine models of NSCLC positively

SUBMITTER: Li R 

PROVIDER: S-EPMC8776246 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature