Dipeptidyl Peptidase 4 Restoration Facilitates Antitumor Immunity in KRAS-LKB1-Mutant Lung Cancer.

ABSTRACT: KRAS proto-oncogene, GTPase (KRAS)-liver kinase B1 (LKB1)-mutant (KL) non-small cell lung cancer (NSCLC), characterized by a profoundly immunosuppressive tumor microenvironment (TME), is highly resistant to immune checkpoint inhibitors. Despite their high tumor mutation burden, KL tumors exhibit low expression of PD-L1, reduced immune cell infiltration, and suppressed immune signaling pathways. Systematic genome analyses revealed that LKB1 loss suppresses dipeptidyl peptidase 4 (DPP4) expression and activity in KRAS-mutant lung cancer. The therapeutic potential of restoring DPP4 function to improve the immune response in KL lung cancer was evaluated using patient-derived tumor samples and syngeneic mouse models. Restoration of DPP4 expression reprogrammed the TME and significantly increase

SUBMITTER: Tenma T 

PROVIDER: S-EPMC12709056 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature