The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response

Autor: Merav Cohen, Amir Giladi, Oren Barboy, Pauline Hamon, Baoguo Li, Mor Zada, Anna Gurevich-Shapiro, Cristian Gabriel Beccaria, Eyal David, Barbara B. Maier, Mark Buckup, Iris Kamer, Aleksandra Deczkowska, Jessica Le Berichel, Jair Bar, Matteo Iannacone, Amos Tanay, Miriam Merad, Ido Amit
Přispěvatelé: Weizmann Institute of Science [Rehovot, Israël], Sackler School of Medicine, Tel Aviv University (TAU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), IRCCS San Raffaele Scientific Institute [Milan, Italie], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Chaim Sheba Medical Center, Interactions cerveau-immunité - Brain-immune communication, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), We thank T. Wiesel for artwork and the Dean’s Flow Cytometry CORE and Biorepository and Pathology CoRE Laboratory of the Icahn School of Medicine at Mount Sinai. The research of I.A. and A.T. is supported by the Seed Networks for the Human Cell Atlas of the Chan Zuckerberg Initiative and by Merck KGaA, Darmstadt. I.A. is an Eden and Steven Romick Professorial Chair, supported by the HHMI International Scholar Award, the European Research Council Consolidator grant (no. 724471-HemTree2.0), an MRA Established Investigator award (no. 509044), DFG (no. SFB/TRR167), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, the Helen and Martin Kimmel awards for innovative investigation and the SCA award of the Wolfson Foundation and Family Charitable Trust. The Thompson Family Foundation Alzheimer’s Research Fund and the Adelis Foundation also provided support. The laboratory of A.T. is supported by the European Research Council (no. 724824), the I-CORE for chromatin and RNA regulation, a grant from the Israel Science Foundation and a grant from the Kahn Foundation. A.T. is a Kimmel investigator. The laboratory of M.M. is supported by R01 CA257195, R01 CA254104 and Samuel Waxman Cancer Research Foundation. A.G. is funded by the Rothschild Postdoctoral Fellowship of the Yad Hanadiv Foundation., European Project: 724471,ERC-2016-COG,HemTree2.0(2017), European Project: 724824,scAssembly
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Nature Cancer
Nature Cancer, 2022, 3 (3), pp.303-317. ⟨10.1038/s43018-022-00338-5⟩
ISSN: 2662-1347
Popis: Comment in: DePICting T cell-APC crosstalk in cancer. Zhang T, Dong C. Nat Cancer. 2022 Mar;3(3):265-267. doi: 10.1038/s43018-022-00345-6. PMID: 35352059 No abstract available.; International audience; Despite their key regulatory role and therapeutic potency, the molecular signatures of interactions between T cells and antigen-presenting myeloid cells within the tumor microenvironment remain poorly characterized. Here, we systematically characterize these interactions using RNA sequencing of physically interacting cells (PIC-seq) and find that CD4+PD-1+CXCL13+ T cells are a major interacting hub with antigen-presenting cells in the tumor microenvironment of human non-small cell lung carcinoma. We define this clonally expanded, tumor-specific and conserved T-cell subset as T-helper tumor (Tht) cells. Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4+ T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht-dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.
Databáze: OpenAIRE
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