Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer.

ABSTRACT: Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success in other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell therapy. Mechanisms driving immunosuppression and poor T-cell infiltration in PDA are incompletely understood. Here, we use genetically engineered mouse models of PDA that recapitulate hallmarks of human disease to demonstrate that CD40 pathway activation is required for clinical response to radiotherapy and ICB with αCTLA-4 and αPD-1. The combination of an agonist αCD40 antibody, radiotherapy, and dual ICB eradicated irradiated and unirradiated (i.e., abscopal) tumors, generating long-term immunity. Response required T cells and also short-lived myeloid cells and was dependent on the l

SUBMITTER: Rech AJ 

PROVIDER: S-EPMC6415684 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature