Immunogenic cell death in cancer: concept and therapeutic implications

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Abstract

Mammalian cells responding to specific perturbations of homeostasis can undergo a regulated variant of cell death that elicits adaptive immune responses. As immunogenic cell death (ICD) can only occur in a precise cellular and organismal context, it should be conceptually differentiated from instances of immunostimulation or inflammatory responses that do not mechanistically depend on cellular demise. Here, we critically discuss key conceptual and mechanistic aspects of ICD and its implications for cancer (immuno)therapy.

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Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Lorenzo Galluzzi, Ilio Vitale, Stuart A. Aaronson … (2018)

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

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Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

Padmanee Sharma, Siwen Hu-Lieskovan, Jennifer A. Wargo … (2017)

Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.

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Neoantigens in cancer immunotherapy.

Ton N. Schumacher, Robert D. Schreiber (2015)

The clinical relevance of T cells in the control of a diverse set of human cancers is now beyond doubt. However, the nature of the antigens that allow the immune system to distinguish cancer cells from noncancer cells has long remained obscure. Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor in the activity of clinical immunotherapies. These observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens. Copyright © 2015, American Association for the Advancement of Science.

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Author and article information

Contributors

Lorenzo Galluzzi:

ORCID: http://orcid.org/0000-0003-2257-8500

deadoc80@gmail.com

Francesco M. Marincola: fmarincola@gmail.com

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 2 March 2023

Publication date PMC-release: 2 March 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 162

Affiliations

[1 ]GRID grid.5386.8, ISNI 000000041936877X, Department of Radiation Oncology, , Weill Cornell Medical College, ; New York, NY USA

[2 ]GRID grid.5386.8, ISNI 000000041936877X, Sandra and Edward Meyer Cancer Center, ; New York, NY USA

[3 ]GRID grid.5386.8, ISNI 000000041936877X, Caryl and Israel Englander Institute for Precision Medicine, ; New York, NY USA

[4 ]GRID grid.14925.3b, ISNI 0000 0001 2284 9388, Metabolomics and Cell Biology Platforms, , Institut Gustave Roussy, ; Villejuif, France

[5 ]Sonata Therapeutics, Boston, MA USA

[6 ]Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Institut Universitaire de France, Sorbonne Université, Inserm U1138, Paris, France

[7 ]GRID grid.414093.b, ISNI 0000 0001 2183 5849, Institut du Cancer Paris CARPEM, Department of Biology, , Hôpital Européen Georges Pompidou, AP-HP, ; Paris, France

[8 ]GRID grid.418227.a, ISNI 0000 0004 0402 1634, Kite Pharma Inc, ; Santa Monica, CA USA

Author information

Lorenzo Galluzzi http://orcid.org/0000-0003-2257-8500

Article

Publisher ID: 4017

DOI: 10.1186/s12967-023-04017-6

PMC ID: 9979428

PubMed ID: 36864446

SO-VID: 609a828c-d195-45ad-b60d-0641f5ec8489

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 24 January 2023

Date accepted : 8 February 2023

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ScienceOpen disciplines: Medicine

Keywords: antigenicity,car t cells,damps,immune checkpoint inhibitors,pattern recognition receptors,tumor microenvironment

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ScienceOpen disciplines: Medicine

Keywords: antigenicity, car t cells, damps, immune checkpoint inhibitors, pattern recognition receptors, tumor microenvironment

Immunogenic cell death in cancer: concept and therapeutic implications

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cGMP: Generators, Effectors and Therapeutic Implications Conference

Most cited references 85

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

Neoantigens in cancer immunotherapy.

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