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Immunogenic Stress and Death of Cancer Cells in Natural and Therapy-Induced Immunosurveillance

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Oncoimmunology

Abstract

The stimulation of cancer immunosurveillance requires malignant cells to differ from their normal counterparts at two distinct levels. First, cancer cells need to express tumor-associated antigens including neoantigens resulting from somatic mutations, meaning that they are antigenically distinct from parental cells. Second, in response to cell-intrinsic or external stress signals, malignant cells must exhibit or release danger-associated molecular patterns (DAMPs) that function as adjuvant signals. The combination of antigenicity and adjuvanticity results in immunogenicity. Some widely used chemotherapeutics, as well as radiotherapy, can stimulate immunogenic cell death (ICD) to set off an anticancer immune response accounting for long-term therapeutic responses. Here we discuss DAMPs, such as annexin A1, ATP, calreticulin, HMGB1, and type-1 interferons, which are exposed or released from stressed and dying cancer cells in response to ICD inducers and the signal transduction pathways leading to their activation. ICD-associated DAMPs act on receptors that are mostly expressed by immune cells, allowing for the orchestration of an intratumoral immune response that involves the recruitment of dendritic cell precursors, the cross-presentation of tumor antigens, and the induction of a cognate anticancer immune response mediated by interferon-γ producing CD8+ T cells. Failure to emit DAMPs due to cancer cell-intrinsic defects or failure to perceive DAMPs due to mutations or inactivation of the receptors required for their perception (such as the annexin A1 receptor FPR1, the HMGB1 receptor TLR4, or the type-1 interferon receptor IFNAR) weakens anticancer immunosurveillance and has a negative prognostic impact in cancer patients.

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Acknowledgments

GK is supported by the French Ligue contre le Cancer (équipe labellisée); 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; 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 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. Gustave Roussy Comprehensive Cancer Institute, Villejuif, France

    Oliver Kepp, Jonathan Pol, Laurence Zitvogel & Guido Kroemer

  2. INSERM, U1138, Paris, France

    Oliver Kepp, Jonathan Pol & Guido Kroemer

  3. Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France

    Oliver Kepp, Jonathan Pol & Guido Kroemer

  4. Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France

    Oliver Kepp, Jonathan Pol & Guido Kroemer

  5. Université Pierre et Marie Curie/Paris VI, Paris, France

    Oliver Kepp, Jonathan Pol & Guido Kroemer

  6. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France

    Oliver Kepp, Jonathan Pol & Guido Kroemer

  7. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France

    Guido Kroemer

  8. Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden

    Guido Kroemer

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  1. Oliver Kepp
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  3. Laurence Zitvogel
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Correspondence to Oliver Kepp or Guido Kroemer .

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  1. Gustave Roussy Cancer Center , Villejuif Cedex, France

    Laurence Zitvogel

  2. Gustave Roussy Cancer Center , Villejuif Cedex, France

    Guido Kroemer

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Kepp, O., Pol, J., Zitvogel, L., Kroemer, G. (2018). Immunogenic Stress and Death of Cancer Cells in Natural and Therapy-Induced Immunosurveillance. In: Zitvogel, L., Kroemer, G. (eds) Oncoimmunology. Springer, Cham. https://doi.org/10.1007/978-3-319-62431-0_12

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