Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses.

التفاصيل البيبلوغرافية
العنوان:	Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses.
المؤلفون:	Bayerl F; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Meiser P; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Donakonda S; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany; German Center for Infection Research, Munich, Germany., Hirschberger A; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Lacher SB; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Pedde AM; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Hermann CD; Institute of Experimental Oncology, School of Medicine, Technical University of Munich, Munich, Germany., Elewaut A; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Knolle M; Institute for Artificial Intelligence in Medicine & Healthcare, School of Medicine, Technical University of Munich, Munich, Germany., Ramsauer L; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Rudolph TJ; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Grassmann S; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, Munich, Germany., Öllinger R; Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, Germany., Kirchhammer N; Cancer Immunology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland., Trefny M; Cancer Immunology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland., Anton M; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Wohlleber D; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Höchst B; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany., Zaremba A; Department for Dermatology, University Hospital Essen, Essen, Germany., Krüger A; Institute of Experimental Oncology, School of Medicine, Technical University of Munich, Munich, Germany., Rad R; Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, Germany., Obenauf AC; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Schadendorf D; Department for Dermatology, University Hospital Essen, Essen, Germany., Zippelius A; Cancer Immunology, Department of Biomedicine, University and University Hospital Basel, Basel, Switzerland., Buchholz VR; Institute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, Munich, Germany., Schraml BU; Walter-Brendel Center for Experimental Medicine, LMU Munich, Planegg-Martinsried, Germany; Biomedical Center, Institute for Cardiovascular Physiology and Pathophysiology, LMU Munich, Planegg-Martinsried, Germany., Böttcher JP; Institute of Molecular Immunology, School of Medicine, Technical University of Munich, Munich, Germany. Electronic address: j.boettcher@tum.de.
المصدر:	Immunity [Immunity] 2023 Jun 13; Vol. 56 (6), pp. 1341-1358.e11.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE
أسماء مطبوعة:	Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994-
مواضيع طبية MeSH:	Dinoprostone* , Neoplasms*, Humans ; Antibodies ; CD8-Positive T-Lymphocytes ; Dendritic Cells ; Receptors, Prostaglandin E
مستخلص:	Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective anti-cancer immunity is thought to require cDC1s to sustain T cell responses within tumors, but it is poorly understood how this function is regulated and whether its subversion contributes to immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE 2 ) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability to locally orchestrate anti-cancer CD8 ⁺ T cell responses. Mechanistically, cAMP signaling downstream of the PGE 2 -receptors EP2 and EP4 was responsible for the programming of cDC1 dysfunction, which depended on the loss of the transcription factor IRF8. Blockade of the PGE 2 -EP2/EP4-cDC1 axis prevented cDC1 dysfunction in tumors, locally reinvigorated anti-cancer CD8 ⁺ T cell responses, and achieved cancer immune control. In human cDC1s, PGE 2 -induced dysfunction is conserved and associated with poor cancer patient prognosis. Our findings reveal a cDC1-dependent intratumoral checkpoint for anti-cancer immunity that is targeted by PGE 2 for immune evasion. Competing Interests: Declaration of interests The authors declare that they have no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
التعليقات:	Comment in: Immunity. 2023 Jun 13;56(6):1165-1167. (PMID: 37315532)
فهرسة مساهمة:	Keywords: T cells; cancer immunotherapy; dendritic cells; immune evasion; prostaglandin E2; tumor microenvironment
المشرفين على المادة:	K7Q1JQR04M (Dinoprostone) 0 (Antibodies) 0 (Receptors, Prostaglandin E)
تواريخ الأحداث:	Date Created: 20230614 Date Completed: 20230616 Latest Revision: 20230619
رمز التحديث:	20240628
DOI:	10.1016/j.immuni.2023.05.011
PMID:	37315536
قاعدة البيانات:	MEDLINE

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