Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Calidi Biotherapeutics San Diego California USA

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki Helsinki Finland

Candiolo Cancer Institute FPO IRCCS Candiolo Italy

Caryl and Israel Englander Institute for Precision Medicine New York City New York USA

Cell Death Research and Therapy Laboratory Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium

Center of Clinical Investigations in Biotherapies of Cancer 1428 Villejuif France

Centre de Recherche du Centre Hospitalier de l'Université de Montréal Montréal Quebec City Canada

Centro de Investigação Translacional em Oncologia LIM24 Instituto do Câncer do Estado de São Paulo Faculdade de Medicina Universidade de São Paulo São Paulo Brasil

Comprehensive Cancer Center Helsinki University Hospital Helsinki Finland

Comprehensive Cancer Center Yale University School of Medicine New Haven Connecticut USA

Department of Bioengineering University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Department of Biomedical Molecular Biology Ghent University Ghent Belgium

Department of Dermatology Yale School of Medicine New Haven Connecticut USA

Department of Immunology Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Immunology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Department of Medical Biology University of Tromsø Tromsø Norway

Department of Medicine Memorial Sloan Kettering Cancer Center New York City New York USA

Department of Medicine Weill Cornell Medical College New York City New York USA

Department of Oncology and Molecular Medicine Istituto Superiore di Sanità Rome Italy

Department of Oncology University of Melbourne Parkville Victoria Australia

Department of Oncology University of Torino Torino Italy

Department of Pathology and Laboratory Medicine Weill Cornell Medical College New York City New York USA

Department of Pharmacology and Pathology University of California at San Diego School of Medicine La Jolla California USA

Department of Radiation Oncology Gustave Roussy Cancer Campus Villejuif France

Department of Radiation Oncology Weill Cornell Medical College New York City New York USA

Department of Surgery University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Department of Surgery UT Southwestern Medical Center Dallas Texas USA

Division of Radiotherapy and Imaging The Institute of Cancer Research London UK

Division of Research and Clinical Medicine Peter MacCallum Cancer Centre Melbourne Victoria Australia

Division of Surgical Oncology Massachusetts General Hospital Boston Massachusetts USA

Equipe 11 labellisée Ligue contre le Cancer Centre de Recherche des Cordeliers Paris France

Equipe labellisée par la Ligue contre le cancer Gustave Roussy Villejuif France

ESSA Pharmaceuticals South San Francisco California USA

Faculté de Pharmacie de l'Université de Montréal Montréal Quebec City Canada

Faculty of Medicine University of Paris Sud Paris Saclay Le Kremlin Bicêtre France

Gustave Roussy Comprehensive Cancer Institute Villejuif France

Hematology and Cell Therapy Clinica Universidad de Navarra Pamplona Spain

Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York City New York USA

Humanitas Clinical and Research Center IRCCS Rozzano Italy

Humanitas University Department of Biomedical Sciences Pieve Emanuele Milan Italy

IIGM Italian Institute for Genomic Medicine c o IRCSS Candiolo Torino Italy

Immun Onkologisches Zentrum Köln Cologne Germany

Immunogenomics and Precision Oncology Platform Memorial Sloan Kettering Cancer Center New York City New York USA

Immunology in Cancer and Infection Laboratory QIMR Berghofer Medical Research Institute Herston Queensland Australia

INSERM Molecular Radiotherapy and therapeutic innovation U1030 Molecular Radiotherapy Gustave Roussy Cancer Campus Villejuif France

INSERM U1015 Villejuif France

INSERM U1138 Paris France

Institut du Cancer de Montréal Montréal Quebec City Canada

Interdepartmental Research Center of Molecular Biotechnology University of Torino Torino Italy

iRepertoire Inc Huntsville Alabama USA

Istituto di Patologia Generale Università Cattolica del Sacro Cuore Rome Italy

Karolinska Institute Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Laboratory of Tumor Immunology and Biology National Cancer Institute Center for Cancer Research National Institutes of Health Bethesda Maryland USA

Ludwig Collaborative and Swim Across America Laboratory MSKCC New York City New York USA

Ludwig Institute for Cancer Research and Department of Oncology University of Lausanne Lausanne Switzerland

Lytix Biopharma Oslo Norway

McMaster University Hamilton Ontario Canada

Merck and Co Inc Kenilworth New Jersey USA

Metabolomics and Cell Biology Platforms Gustave Roussy Comprehensive Cancer Institute Villejuif France

Methusalem program Ghent University Ghent Belgium

NanoString Technologies Seattle Washington USA

Parker Institute for Cancer Immunotherapy MSKCC New York City New York USA

Pôle de Biologie Hôpital Européen Georges Pompidou AP HP Paris France

Program of Immunology and Immunotherapy Centro de Investigación Médica Aplicada University of Navarra Pamplona Spain

Refuge Biotechnologies Menlo Park California USA

Replimune Inc Woburn Massachusetts USA

Sandra and Edward Meyer Cancer Center New York City New York USA

SIRIC SOCRATES DHU Torino Faculté de Medecine Université Paris Saclay Kremlin Bicêtre France

Sorbonne Université Paris France

Sotio Prague Czech Republic

Suzhou Institute for Systems Medicine Chinese Academy of Medical Sciences Suzhou China

The Institute of Cancer Research London UK

The Royal Marsden Hospital Institute of Cancer Research National Institute for Health Biomedical Research Centre London UK

Universitätsklinikum Erlangen Erlangen Germany

Université de Paris Paris France

University of Manchester NIHR Manchester Biomedical Research Centre Christie Hospital Manchester UK

UOSD Immunology and Immunotherapy Unit IRCCS Regina Elena National Cancer Institute Rome Italy

VIB Center for Inflammation Research Ghent Belgium

VIB KU Leuven Center for Cancer Biology KU Leuevn Leuven Belgium

Weill Cornell Medical College New York City New York USA

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$a Consensus guidelines for the definition, detection and interpretation of immunogenic cell death / $c L. Galluzzi, I. Vitale, S. Warren, S. Adjemian, P. Agostinis, AB. Martinez, TA. Chan, G. Coukos, S. Demaria, E. Deutsch, D. Draganov, RL. Edelson, SC. Formenti, J. Fucikova, L. Gabriele, US. Gaipl, SR. Gameiro, AD. Garg, E. Golden, J. Han, KJ. Harrington, A. Hemminki, JW. Hodge, DMS. Hossain, T. Illidge, M. Karin, HL. Kaufman, O. Kepp, G. Kroemer, JJ. Lasarte, S. Loi, MT. Lotze, G. Manic, T. Merghoub, AA. Melcher, KL. Mossman, F. Prosper, Ø. Rekdal, M. Rescigno, C. Riganti, A. Sistigu, MJ. Smyth, R. Spisek, J. Stagg, BE. Strauss, D. Tang, K. Tatsuno, SW. van Gool, P. Vandenabeele, T. Yamazaki, D. Zamarin, L. Zitvogel, A. Cesano, FM. Marincola

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$a Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

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