Overcoming microenvironmental resistance to PD-1 blockade in genetically engineered lung cancer models.

ABSTRACT: Immune checkpoint blockade (ICB) with PD-1 or PD-L1 antibodies has been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients respond, and sustained remissions are rare. Both chemotherapy and antiangiogenic drugs may improve the efficacy of ICB in mouse tumor models and patients with cancer. Here, we used genetically engineered mouse models of KrasG12D/+;p53-/- NSCLC, including a mismatch repair-deficient variant (KrasG12D/+;p53-/-;Msh2-/-) with higher mutational burden, and longitudinal imaging to study tumor response and resistance to combinations of ICB, antiangiogenic therapy, and chemotherapy. Antiangiogenic blockade of vascular endothelial growth factor A and angiopoietin-2 markedly slowed progression of autochthonous lung tumors, but

SUBMITTER: Martinez-Usatorre A 

PROVIDER: S-EPMC7612153 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature