AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1⁺ CD8 T cells.

ABSTRACT: Mutations in STK11/LKB1 in non-small cell lung cancer (NSCLC) are associated with poor patient responses to immune checkpoint blockade (ICB), and introduction of a Stk11/Lkb1 (L) mutation into murine lung adenocarcinomas driven by mutant Kras and Trp53 loss (KP) resulted in an ICB refractory syngeneic KPL tumor. Mechanistically this occurred because KPL mutant NSCLCs lacked TCF1-expressing CD8 T cells, a phenotype recapitulated in human STK11/LKB1 mutant NSCLCs. Systemic inhibition of Axl results in increased type I interferon secretion from dendritic cells that expanded tumor-associated TCF1⁺PD-1⁺CD8 T cells, restoring therapeutic response to PD-1 ICB in KPL tumors. This was observed in syngeneic i

SUBMITTER: Li H 

PROVIDER: S-EPMC9040166 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature