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      Radiochemotherapy-induced elevations of plasma HMGB1 levels predict therapeutic responses in cancer patients

      editorial
      Author(s): a , b , c , a , b
      Publication date (Electronic, pub):
      Publication date (Electronic, collection):
      Journal: Oncoimmunology
      Publisher: Taylor & Francis
      Keywords: Immunotherapy, immunogenic cell death, damage-associated molecular pattern

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          ABSTRACT

          High mobility group B1 (HMGB1) is a protein that is released from dying cancer cells in the context of immunogenic cell death (ICD). A recent study performed on patients with head and neck squamous cell carcinomas (HNSCC) reports that a chemoradiotherapy-induced increase in circulating HMGB1 levels predicts favorable outcome, echoing prior studies on neoadjuvant treatment of breast and rectal cancer in which the dynamics of HMGB1 plasma levels also have prognostic value. Hence, a therapy-induced rise in HMGB1 may be interpreted as a clinical sign of ICD and therapeutic response.

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          Immunogenic cell death in cancer and infectious disease

          Lorenzo Galluzzi, Aitziber Buqué, Oliver Kepp … (2016)
          Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process?
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            Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.

            Lionel Apetoh, Francois Ghiringhelli, Antoine Tesniere … (2007)
            Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.
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              Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

              Lorenzo Galluzzi, Ilio Vitale, Sarah Warren … (2020)
              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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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncoimmunology
                Journal ID (iso-abbrev): Oncoimmunology
                Title: Oncoimmunology
                Publisher: Taylor & Francis
                ISSN (Print): 2162-4011
                ISSN (Electronic): 2162-402X
                Publication date (Electronic, pub): 23 November 2021
                Publication date (Electronic, collection): 2021
                Publication date PMC-release: 23 November 2021
                Volume: 10
                Issue: 1
                Electronic Location Identifier: 2005859
                Affiliations
                [a ]Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay; , Villejuif, France
                [b ]Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138 and CNRS SNC 5096, Institut Universitaire de France; , Paris, France
                [c ]Pôle de Biologie, Institut du Cancer Paris Carpem, APHP, Hôpital Européen Georges Pompidou; , Paris, France
                Author notes
                CONTACT Oliver Kepp captain.olsen@ 123456gmail.com Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Center, Université Paris Saclay; , 39 Rue Camille Desmoulins, Villejuif 94800, France
                Author information
                https://orcid.org/0000-0002-9334-4405
                https://orcid.org/0000-0002-6081-9558
                Article
                Publisher ID: 2005859
                DOI: 10.1080/2162402X.2021.2005859
                PMC ID: 8632107
                PubMed ID: 34858731
                SO-VID: 71260933-7960-4f60-8018-3857a2880686
                Copyright © © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 1, References: 10, Pages: 1
                Categories
                Subject: Editorial
                Subject: Editorial

                ScienceOpen disciplines: Immunology
                Keywords: immunotherapy,immunogenic cell death,damage-associated molecular pattern
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: immunotherapy, immunogenic cell death, damage-associated molecular pattern

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