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| Home > Publications database > CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment. |
| Home > Publications database > CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment. |
| Journal Article | DKFZ-2023-00114 |
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2023
Nature Publishing Group UK
[London]
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Please use a persistent id in citations: doi:10.1038/s41467-022-35615-5
Abstract: 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.
Keyword(s): Humans (MeSH) ; CD8-Positive T-Lymphocytes (MeSH) ; Neoplasms: metabolism (MeSH) ; Antigen Presentation (MeSH) ; T-Lymphocytes, Cytotoxic (MeSH) ; Dendritic Cells (MeSH) ; T-Lymphocytes, Helper-Inducer: metabolism (MeSH) ; Tumor Microenvironment (MeSH)
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