CD103⁺ cDC1 and endogenous CD8⁺ T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function.

ABSTRACT: While effective in specific settings, adoptive chimeric antigen receptor (CAR) T cell therapy for cancer requires further improvement and optimization. Our previous results show that CD40L-overexpressing CAR T cells mobilize endogenous immune effectors, resulting in improved antitumor immunity. However, the cell populations required for this protective effect remain to be identified. Here we show, by analyzing Batf3^-/- mice lacking the CD103⁺ conventional dendritic cell type 1 (cDC1) subpopulation important for antigen cross-presentation, that CD40L-overexpressing CAR T cells elicit an impaired antitumor response in the absence of cDC1s. We further find that CD40L-overexpressing CAR T cells stimulate tumor-resident CD11b^-CD103^- double-negative (D

SUBMITTER: Kuhn NF 

PROVIDER: S-EPMC7710757 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature