Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment.

ABSTRACT:

Background

KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, the response to immunotherapy is heterogeneous owing to the distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor response to PD-1 blockade whereas the mechanism remains undetermined.

Methods

We explored the specific characteristics of tumor microenvironment (TME) in KL tumors using syngeneic KRAS^G12DLKB1^-/- (KL) and KRAS^G12DTP53^-/- (KP) lung cancer mouse models. The impact of focal adhesion kinase (FAK) inhibitor on KL lung tumors was investigated in vitro and in vivo through evaluation of both KL cell lines and KL lung cancer mouse models.

Results

We identified KL tumors as "immune-cold" tumor

SUBMITTER: Qiao M 

PROVIDER: S-EPMC10826079 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature