%0 Journal Article
%A Lei, Xin
%A Khatri, Indu
%A de Wit, Tom
%A de Rink, Iris
%A Nieuwland, Marja
%A Kerkhoven, Ron
%A van Eenennaam, Hans
%A Sun, Chong
%A Garg, Abhishek D
%A Borst, Jannie
%A Xiao, Yanling
%T CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2023-00114
%P 217
%D 2023
%X Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with patient survival. However, their interaction with CD4+ T-cells to potentially enable the cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact with activated CD4+ T-cells enables human ex vivo cDC1, but no other DC types, to induce a CTL response to cell-associated tumor antigens. Single cell transcriptomics reveals that CD4+ T-cell help uniquely optimizes cDC1 in many functions that support antigen cross-presentation and T-cell priming, while these changes don't apply to other DC types. We robustly identify 'helped' cDC1 in the TME of a multitude of human cancer types by the overlap in their transcriptomic signature with that of recently defined, tumor-infiltrating DC states that prove to be positively prognostic. As predicted from the functional effects of CD4+ T-cell help, the transcriptomic signature of 'helped' cDC1 correlates with tumor infiltration by CTLs and Thelper(h)-1 cells, overall survival and response to PD-1-targeting immunotherapy. These findings reveal a critical role for CD4+ T-cell help in enabling cDC1 function in the TME and may establish the helped cDC1 transcriptomic signature as diagnostic marker in cancer.
%K Humans
%K CD8-Positive T-Lymphocytes
%K Neoplasms: metabolism
%K Antigen Presentation
%K T-Lymphocytes, Cytotoxic
%K Dendritic Cells
%K T-Lymphocytes, Helper-Inducer: metabolism
%K Tumor Microenvironment
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36639382
%2 pmc:PMC9839676
%R 10.1038/s41467-022-35615-5
%U https://inrepo02.dkfz.de/record/210385