CD103(+) cDC1 and endogenous CD8(+) T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function Journal Article


Authors: Kuhn, N. F.; Lopez, A. V.; Li, X.; Cai, W.; Daniyan, A. F.; Brentjens, R. J.
Article Title: 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 (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. © 2020, The Author(s).
Keywords: gene expression; antigen; immunity; tumor; optimization; cell; cancer
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-12-02
Start Page: 6171
Language: English
DOI: 10.1038/s41467-020-19833-3
PUBMED: 33268774
PROVIDER: scopus
PMCID: PMC7710757
DOI/URL:
Notes: Article -- Export Date: 4 January 2021 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    267 Brentjens
  2. Anthony   Daniyan
    18 Daniyan
  3. Nicholas Frederik Kuhn
    3 Kuhn
  4. Xinghuo Li
    4 Li
  5. Andrea V Lopez
    7 Lopez
  6. Winson Cai
    1 Cai