The term 'immunogenic cell death' (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the preclinical and clinical development of ICD-eliciting chemotherapy as partner for immunotherapy, with a focus on trials assessing efficacy in the context of immunomonitoring.

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

Department of Haematology UZ Leuven and Department of Human Genetics KU Leuven Leuven Belgium

Department of Oncology KU Leuven Leuven Belgium UZ Leuven Leuven Belgium

Department of Radiation Oncology Weill Cornell Medical College New York NY USA Sandra and Edward Meyer Cancer Center New York NY USA Caryl and Israel Englander Institute for Precision Medicine New York NY USA Department of Dermatology Yale School of Medicine New Haven CT USA Université de Paris Paris France

Equipe labellisée par la Ligue contre le cancer Centre de Recherche des Cordeliers Université de Paris Sorbonne Université INSERM U1138 Paris France Metabolomics and Cell Biology Platforms Gustave Roussy Comprehensive Cancer Institute Villejuif France Pôle de Biologie Hôpital Européen Georges Pompidou AP HP Paris France Suzhou Institute for Systems Medicine Chinese Academy of Medical Sciences Suzhou China Department of Women's and Children's Health Karolinska University Hospital Stockholm Sweden

Gustave Roussy Comprehensive Cancer Institute Villejuif France INSERM U1015 Villejuif France Center of Clinical Investigations in Biotherapies of Cancer 1428 Villejuif France Université Paris Sud Paris XI Le Kremlin Bicêtre France

Maastricht University Medical Center Department of Radiation Oncology GROW School for Oncology and Developmental Biology Maastricht Netherlands

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

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