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000210385 041__ $$aEnglish
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000210385 1001_ $$aLei, Xin$$b0
000210385 245__ $$aCD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.
000210385 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000210385 520__ $$aDespite 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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000210385 650_2 $$2MeSH$$aHumans
000210385 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes
000210385 650_2 $$2MeSH$$aNeoplasms: metabolism
000210385 650_2 $$2MeSH$$aAntigen Presentation
000210385 650_2 $$2MeSH$$aT-Lymphocytes, Cytotoxic
000210385 650_2 $$2MeSH$$aDendritic Cells
000210385 650_2 $$2MeSH$$aT-Lymphocytes, Helper-Inducer: metabolism
000210385 650_2 $$2MeSH$$aTumor Microenvironment
000210385 7001_ $$00000-0002-7993-1953$$aKhatri, Indu$$b1
000210385 7001_ $$ade Wit, Tom$$b2
000210385 7001_ $$ade Rink, Iris$$b3
000210385 7001_ $$aNieuwland, Marja$$b4
000210385 7001_ $$aKerkhoven, Ron$$b5
000210385 7001_ $$avan Eenennaam, Hans$$b6
000210385 7001_ $$0P:(DE-He78)ef40d75e5564c492ee57b4262fc016fe$$aSun, Chong$$b7$$udkfz
000210385 7001_ $$00000-0002-9976-9922$$aGarg, Abhishek D$$b8
000210385 7001_ $$00000-0002-8043-5009$$aBorst, Jannie$$b9
000210385 7001_ $$aXiao, Yanling$$b10
000210385 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-022-35615-5$$gVol. 14, no. 1, p. 217$$n1$$p217$$tNature Communications$$v14$$x2041-1723$$y2023
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