Tumor-infiltrating mast cells confer resistance to immunotherapy in pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD8⁺ T effector cells expressing granzyme B and dramatic survival benefit un

SUBMITTER: Ma Y 

PROVIDER: S-EPMC11514315 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature