| First Author | Kuhn NF | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 6171 |
| PubMed ID | 33268774 | Mgi Jnum | J:299925 |
| Mgi Id | MGI:6490832 | Doi | 10.1038/s41467-020-19833-3 |
| Citation | Kuhn NF, et al. (2020) CD103(+) cDC1 and endogenous CD8(+) T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function. Nat Commun 11(1):6171 |
| abstractText | 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 (DN) cDCs to proliferate and differentiate into cDC1s in wild-type mice. Finally, re-challenge experiments show that endogenous CD8(+) T cells are required for protective antitumor memory in this setting. Our findings thus demonstrate the stimulatory effect of CD40L-overexpressing CAR T cells on innate and adaptive immune cells, and provide a rationale for using CD40L-overexpressing CAR T cells to improve immunotherapy responses. |
