Although clinical data suggest remarkable promise for targeting programmed cell 
death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small-cell lung 
cancer (NSCLC), it is still largely undetermined which subtype of patients will 
be responsive to checkpoint blockade. In the present study, we explored whether 
PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog (KRAS), 
which is frequently mutated in NSCLC and results in poor prognosis and low 
survival rates. We verified that PD-L1 levels were dramatically increased in 
KRAS mutant cell lines, particularly in NCI-H441 cells with KRAS G12V mutation. 
Overexpression of KRAS G12V remarkably elevated PD-L1 messenger RNA and protein 
levels, while suppression of KRAS G12V led to decreased PD-L1 levels in NCI-H441 
cells. Consistently, higher levels of PD-L1 were observed in KRAS-mutated 
tissues as well as tumor tissues-derived CD4+ and CD8+ T cells using a tumor 
xenograft in B-NDG mice. Mechanically, both in vitro and in vivo assays found 
that KRAS G12V upregulated PD-L1 via regulating the progression of 
epithelial-to-mesenchymal transition (EMT). Moreover, pembrolizumab activated 
the antitumor activity and decreased tumor growth with KRAS G12V mutated NSCLC. 
This study demonstrates that KRAS G12V mutation could induce PD-L1 expression 
and promote immune escape via transforming growth factor-β/EMT signaling pathway 
in KRAS-mutant NSCLC, providing a potential therapeutic approach for NSCLC 
harboring KRAS mutations.