Home > Publications database > CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment. > print

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024 7 _ |a 10.1038/s41467-022-35615-5
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041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Lei, Xin
|b 0
245 _ _ |a CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.
260 _ _ |a [London]
|c 2023
|b Nature Publishing Group UK
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520 _ _ |a 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.
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a CD8-Positive T-Lymphocytes
|2 MeSH
650 _ 2 |a Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Antigen Presentation
|2 MeSH
650 _ 2 |a T-Lymphocytes, Cytotoxic
|2 MeSH
650 _ 2 |a Dendritic Cells
|2 MeSH
650 _ 2 |a T-Lymphocytes, Helper-Inducer: metabolism
|2 MeSH
650 _ 2 |a Tumor Microenvironment
|2 MeSH
700 1 _ |a Khatri, Indu
|0 0000-0002-7993-1953
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700 1 _ |a de Wit, Tom
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700 1 _ |a de Rink, Iris
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700 1 _ |a Nieuwland, Marja
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700 1 _ |a Kerkhoven, Ron
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700 1 _ |a van Eenennaam, Hans
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700 1 _ |a Sun, Chong
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700 1 _ |a Garg, Abhishek D
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700 1 _ |a Borst, Jannie
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700 1 _ |a Xiao, Yanling
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773 _ _ |a 10.1038/s41467-022-35615-5
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