Gain-of-function p53^R172H mutation drives accumulation of neutrophils in pancreatic tumors, promoting resistance to immunotherapy.

ABSTRACT: Tumor genotype can influence the immune microenvironment, which plays a critical role in cancer development and therapy resistance. However, the immune effects of gain-of-function Trp53 mutations have not been defined in pancreatic cancer. We compare the immune profiles generated by Kras^G12D-mutated mouse pancreatic ductal epithelial cells (PDECs) engineered genetically to express the Trp53^R172H mutation with their p53 wild-type control. Kras^G12D/+;Trp53^R172H/+ tumors have a distinct immune profile characterized by an influx of CD11b⁺Ly6G⁺ neutrophils and concomitant decreases in CD3⁺ T cells, CD8⁺ T cells, and CD4⁺ T helper 1 cells. Knockdown of CXCL2, a neutrophil chemokine, in the tumor ep

SUBMITTER: Siolas D 

PROVIDER: S-EPMC8687588 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature