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Immunosuppressive cell death in cancer

Nature Reviews Immunology volume 17, page 402 (2017)Cite this article

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In our recent Review (Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017))1, we discussed the molecular and cellular processes through which the death of infected and malignant cells can initiate an adaptive immune response against dead cell-associated antigens (in immunocompetent syngeneic hosts). This process, which is commonly known as immunogenic cell death (ICD), involves: first, the timely release of danger signals from dying cells secondary to the activation of adaptive stress responses, which include the unfolded protein response2 and autophagy3; and second, the proficient detection of such signals by innate and adaptive compartments of the immune system4. Preclinical and clinical data support the notion that ICD has prominent pathophysiological implications in the context of cancer therapy1. Indeed, molecular defects in the mechanisms that underlie the release or detection of ICD-associated danger signals have been associated with poor disease outcome in multiple cohorts of patients with cancer5,6,7.

In their Correspondence (Immunosuppressive cell death in cancer. Nat. Rev. Immunol. doi: 10.1038/nri.2017.46 (2017)), Xia and collaborators correctly point out that the demise of malignant cells responding to chemotherapy or radiation therapy frequently fails to elicit anticancer immunity in preclinical and clinical scenarios. Indeed, far too often neoplasms progress as they harness strategies to evade or suppress potential ICD-driven immune responses8,9,10. Furthermore, chemotherapy and radiation therapy are often administered to patients at high doses, which have immunosuppressive rather than immunostimulatory effects11,12,13. Thus, cancer cell death — as elicited in patients by conventional chemotherapeutic and radiotherapeutic regimens — is intrinsically prone to be overlooked by the immune system or to stimulate immune tolerance. Based on this postulate, Xia and collaborators propose that combinatorial antineoplastic strategies should be aimed at maximizing the number of cancer cells that succumb to treatment.

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Acknowledgements

L.G. is supported by a start-up intramural grant from the Department of Radiation Oncology of Weill Cornell Medical College, New York, NY, USA, and Sotio a.c., Prague, Czech Replublic. A.B., O.K. and G.K. are supported by the French Ligue contre le Cancer (équipe labellisée); the French Agence National de la Recherche (ANR) — Projets Blancs; ANR under the frame of E-Rare-2 (the ERA-Net for Research on Rare Diseases); Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; the French Institut National du Cancer (INCa); Institut Universitaire de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LeDucq Foundation; the LabEx Immuno-Oncology; the Sites de Recherche Intégrée sur le Cancer (SIRIC) Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).

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Authors and Affiliations

  1. Lorenzo Galluzzi is at the Department of Radiation Oncology, Weill Cornell Medical College, New York, New York 10065, USA,

    Lorenzo Galluzzi

  2. the Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.,

    Lorenzo Galluzzi

  3. Aitziber Buqué and Oliver Kepp are at Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; INSERM, U1138, 75006 Paris, France; and at Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France.,

    Aitziber Buqué & Oliver Kepp

  4. at Université Pierre et Marie Curie/Paris VI, 75006 Paris, France,

    Aitziber Buqué & Oliver Kepp

  5. Laurence Zitvogel is at Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; the Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, 94805 Villejuif, France; and the Université Paris Sud/Paris XI, 94270 Le Kremlin-Bicêtre, France.,

    Laurence Zitvogel

  6. INSERM, U1015, 94805 Villejuif, France,

    Laurence Zitvogel

  7. Department of Women's and Children's Health, Guido Kroemer is at Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; at INSERM, U1138, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France; Karolinska Institute, Karolinska University Hospital, 17176 Stockholm, Sweden; and at Pôle de Biologie, Hopitâl Européen George Pompidou, AP-HP; 75015 Paris, France.,

    Guido Kroemer

  8. Université Pierre et Marie Curie/Paris VI, 75006 Paris,

    Guido Kroemer

Authors
  1. Lorenzo Galluzzi
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  2. Aitziber Buqué
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  3. Oliver Kepp
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  4. Laurence Zitvogel
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  5. Guido Kroemer
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Corresponding authors

Correspondence to Lorenzo Galluzzi or Guido Kroemer.

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Galluzzi, L., Buqué, A., Kepp, O. et al. Immunosuppressive cell death in cancer. Nat Rev Immunol 17, 402 (2017). https://doi.org/10.1038/nri.2017.48

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