A distinct stimulatory cDC1 subpopulation amplifies CD8 + T cell responses in tumors for protective anti-cancer immunity.

Autor:	Meiser P; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Knolle MA; Institute for Artificial Intelligence in Medicine & Healthcare, School of Medicine, TUM, Munich, Germany; Institute for Diagnostic and Interventional Radiology, School of Medicine, TUM, Munich, Germany; Department of Computing, Imperial College London, London, UK., Hirschberger A; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., de Almeida GP; Institute of Animal Physiology and Immunology, School of Life Science, TUM, Freising, Germany; Institute of Virology, School of Medicine, TUM, Munich, Germany., Bayerl F; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Lacher S; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Pedde AM; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Flommersfeld S; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, TUM, Munich, Germany., Hönninger J; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, TUM, Munich, Germany., Stark L; Department of Otolaryngology Head and Neck Surgery, School of Medicine, TUM, Munich, Germany., Stögbauer F; Institute of Pathology, School of Medicine, TUM, Munich, Germany., Anton M; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Wirth M; Department of Otolaryngology Head and Neck Surgery, School of Medicine, TUM, Munich, Germany., Wohlleber D; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany., Steiger K; Institute of Pathology, School of Medicine, TUM, Munich, Germany; Comparative Experimental Pathology, School of Medicine, TUM, Munich, Germany; German Cancer Consortium, partner site Munich, Munich, Germany., Buchholz VR; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, TUM, Munich, Germany., Wollenberg B; Department of Otolaryngology Head and Neck Surgery, School of Medicine, TUM, Munich, Germany., Zielinski CE; Department of Infection Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany; Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany., Braren R; Institute for Diagnostic and Interventional Radiology, School of Medicine, TUM, Munich, Germany., Rueckert D; Institute for Artificial Intelligence in Medicine & Healthcare, School of Medicine, TUM, Munich, Germany; Department of Computing, Imperial College London, London, UK; Chair for Artificial Intelligence in Medicine and Healthcare, School of Medicine and School of Computation, Information and Technology, Klinikum rechts der Isar, TUM, Munich, Germany., Knolle PA; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany; Institute of Molecular Immunology, School of Life Science, TUM, Freising, Germany; German Center for Infection Research, Munich site, Munich, Germany., Kaissis G; Institute for Artificial Intelligence in Medicine & Healthcare, School of Medicine, TUM, Munich, Germany; Institute for Diagnostic and Interventional Radiology, School of Medicine, TUM, Munich, Germany; Department of Computing, Imperial College London, London, UK., Böttcher JP; Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Munich, Germany. Electronic address: j.boettcher@tum.de.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2023 Aug 14; Vol. 41 (8), pp. 1498-1515.e10. Date of Electronic Publication: 2023 Jul 13.
DOI:	10.1016/j.ccell.2023.06.008
Abstrakt:	Type 1 conventional dendritic cells (cDC1) can support T cell responses within tumors but whether this determines protective versus ineffective anti-cancer immunity is poorly understood. Here, we use imaging-based deep learning to identify intratumoral cDC1-CD8 + T cell clustering as a unique feature of protective anti-cancer immunity. These clusters form selectively in stromal tumor regions and constitute niches in which cDC1 activate TCF1 + stem-like CD8 + T cells. We identify a distinct population of immunostimulatory CCR7 neg cDC1 that produce CXCL9 to promote cluster formation and cross-present tumor antigens within these niches, which is required for intratumoral CD8 + T cell differentiation and expansion and promotes cancer immune control. Similarly, in human cancers, CCR7 neg cDC1 interact with CD8 + T cells in clusters and are associated with patient survival. Our findings reveal an intratumoral phase of the anti-cancer T cell response orchestrated by tumor-residing cDC1 that determines protective versus ineffective immunity and could be exploited for cancer therapy. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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