Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy

Article Article scientifique Article Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy eng 2024-05-02 2024-05-02 author Wang Chen Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. Electronic address: chen.wang.1@unige.ch. 855721 author Zeng Qun Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 404292 Département de pathologie et immunologie (PATIM) author Gul Zeynep Melis Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 989923 Département de pathologie et immunologie (PATIM) author Wang Sisi Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland. 966349 Département de médecine (DEMED) author Pick Robert Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 921203 Département de pathologie et immunologie (PATIM) author Cheng Phil 0000-0003-2940-006X Department of Oncology and Precision Oncology Service, Geneva University Hospitals, University of Geneva, Geneva 1211, Switzerland. 418075 author Bill Ruben Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; AGORA Cancer Research Center, Lausanne 1011, Switzerland; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA 02114, USA. 974134 author Wu Yan Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China. author Naulaerts Stefan Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine, KU Leuven, Leuven 3000, Belgium. author Barnoud Coline 0000-0001-5500-0217 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 823138 author Hsueh Pei-Chun Department of Fundamental Oncology, University of Lausanne, Lausanne 1066, Switzerland; Ludwig Institute for Cancer Research, Lausanne 1005, Switzerland. author Moller Sofie Hedlund Department of Fundamental Oncology, University of Lausanne, Lausanne 1066, Switzerland; Ludwig Institute for Cancer Research, Lausanne 1005, Switzerland. author Cenerenti Mara 0000-0001-6630-0557 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 943132 Département de pathologie et immunologie (PATIM) author Sun Mengzhu 0009-0004-5561-9334 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 919193 Département de pathologie et immunologie (PATIM) author Su Ziyang Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 402588 Département de pathologie et immunologie (PATIM) author Jemelin Stéphane Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland. 116782 Département de pathologie et immunologie (PATIM) author Petrenko Volodymyr Division of Thoracic and Endocrine Surgery, Department of Surgery, Geneva University Hospitals, Geneva 1205, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), Geneva 1211, Switzerland. 712248 author Dibner Charna 0000-0002-4188-803X Division of Thoracic and Endocrine Surgery, Department of Surgery, Geneva University Hospitals, Geneva 1205, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), Geneva 1211, Switzerland. 583541 Département de chirurgie (CHIRU) author Hugues Stéphanie Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; Geneva Centre for Inflammation Research (GCIR), Geneva 1211, Switzerland. 663452 Département de pathologie et immunologie (PATIM) author Jandus Camilla 0000-0002-7405-5747 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; Ludwig Institute for Cancer Research, Lausanne 1005, Switzerland; Geneva Centre for Inflammation Research (GCIR), Geneva 1211, Switzerland. 932821 Département de pathologie et immunologie (PATIM) author Li Zhongwu Key Laboratory of Carcinogenesis and Translational Research, Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China. author Michielin Olivier Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; Department of Oncology and Precision Oncology Service, Geneva University Hospitals, University of Geneva, Geneva 1211, Switzerland. 903944 Département de médecine (DEMED) author Ho Ping-Chih Department of Fundamental Oncology, University of Lausanne, Lausanne 1066, Switzerland; Ludwig Institute for Cancer Research, Lausanne 1005, Switzerland. author Garg Abhishek D Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine, KU Leuven, Leuven 3000, Belgium. author Simonetta Federico Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; Division of Hematology, Department of Oncology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland. 936876 Département de médecine (DEMED) author Pittet Mikaël Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; AGORA Cancer Research Center, Lausanne 1011, Switzerland; Ludwig Institute for Cancer Research, Lausanne 1005, Switzerland; Geneva Centre for Inflammation Research (GCIR), Geneva 1211, Switzerland. 917678 Département de pathologie et immunologie (PATIM) author Scheiermann Christoph 0000-0002-9212-0995 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Translational Research Centre in Onco-Hematology (CRTOH), Geneva 1211, Switzerland; Institute of Genetics and Genomics of Geneva (iGE3), Geneva 1211, Switzerland; Geneva Centre for Inflammation Research (GCIR), Geneva 1211, Switzerland; Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität (LMU) Munich, Planegg-Martinsried 82152, Germany. Electronic address: christoph.scheiermann@unige.ch. 891044 Département de pathologie et immunologie (PATIM) 2690-2702.e17 10.1016/j.cell.2024.04.015 38723627 0092-8674 https://www.sciencedirect.com/science/article/pii/S0092867424004100 The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8<sup>+</sup>T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care. BMAL1 CAR T therapy PD-1 Chronotherapy Circadian Immune checkpoint blockade Immunology Melanoma Tumor-infiltrating leukocyte Dewey 612 Dewey 616.07 Dewey 616 Dewey 617 Dewey 590 57 Département de chirurgie 222 137 Département de pathologie et immunologie 21F 56 Département de médecine 221 134 Département de physiologie cellulaire et métabolisme 21C 23 Institut de génétique et de génomique 0DH false 913 Endocrinologie et horloge circadienne 948 1259 L'influence du rôle du cycle circadien sur l'immunité 995 563 Pathologie et immunologie 906 1309 Ciblage des lymphocytes sécrétant des cytokines 1015 1432 Découverte de biomarqueurs numériques pour l'oncologie de précision 1059 1336 Comprendre et manipuler le système immunitaire pour lutter contre le cancer 1024 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE260641 https://yareta.unige.ch/archives/01496ea3-05cb-4464-8e93-9395ce3b82e4 https://github.com/zqun1/circadian_immune_mouse_melanoma Cell 187 11 c8fcbd63-6f7f-42ec-81a4-4730ddee4ea1 Article (Published version) Public 1-s2.0-S0092867424004100-main1.pdf 8700614 application/pdf CC BY-4.0 fc5ade5b9041b1d86ea91ba4fd25a173aa5ba7230b045b4aee8d78521f759146 6e3f5683-b64e-4f84-9478-cd736d78176f Supplemental data Public ScienceDirect_files_12Jun2024_08-08.zip 1462438 application/zip b554e8e953bd2d996dc62a548e7c2aaefa2970eeb72c3f27c772623216a98cca Vignette Public 1-s2.0-S0092867424004100-fx1.jpg 190747 image/png openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Centres et instituts / Institut de génétique et de génomique

Title	Published in	Year	Views	Downloads

Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy	Cell	2024	643	141
Circadian rhythms in anticancer immunity : mechanisms and treatment opportunities	Annual review of immunology	2024	29	15

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