CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer.

ABSTRACT: Cancer immunotherapies are more effective in tumors with robust T cell infiltrates, but mechanisms to convert T cell-devoid tumors with active immunosuppression to those capable of recruiting T cells remain incompletely understood. Here, using genetically engineered mouse models of pancreatic ductal adenocarcinoma (PDA), we demonstrate that a single dose of agonistic CD40 antibody with chemotherapy rendered PDA susceptible to T cell-dependent destruction and potentiated durable remissions. CD40 stimulation caused a clonal expansion of T cells in the tumor, but the addition of chemotherapy optimized myeloid activation and T cell function. Although recent data highlight the requirement for innate sensors in cancer immunity, these canonical pathways-including TLRs, inflammasome, and type I in

SUBMITTER: Byrne KT 

PROVIDER: S-EPMC4917417 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature