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CANCER IMMUNOLOGY

Immuno-epigenetic escape of cancer stem cells

Nature Immunology volume 23, pages 1300–1302 (2022)Cite this article

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The net effect of type I interferon (IFN-I) signaling on tumor control depends on various factors, including the potential engagement of adaptive anticancer immunity. New findings delineate a targetable epigenetic mechanism by which suboptimal IFN-I signaling promotes tumor progression in the context of cancer stem cell expansion and immunoevasion.

Type 1 interferon (IFN-I) consists of a family of immunostimulatory cytokines that are required for optimal antiviral responses1, as well as for the immunogenic perception of cancer cell death2. In this issue of Nature Immunology, Musella et al.3 describe a setting in which IFN-I signaling elicited by immunogenic cell death (ICD) fails to drive therapeutically relevant anticancer immunity and instead promotes tumor progression via the expansion of a cancer stem cell (CSC) population with immunoevasive properties.

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Fig. 1: Suboptimal ICD induction coupled to CSC expansion by IFN-I-driven KDM1B activation.

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Authors and Affiliations

  1. Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA

    Lorenzo Galluzzi

  2. Sandra and Edward Meyer Cancer Center, New York, NY, USA

    Lorenzo Galluzzi

  3. Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA

    Lorenzo Galluzzi

  4. Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France

    Guido Kroemer

  5. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Université Paris Saclay, Villejuif, France

    Guido Kroemer

  6. Institut du Cancer Paris CARPEM, Department of Biology, APHP, Hôpital Européen Georges Pompidou, Paris, France

    Guido Kroemer

Authors
  1. Lorenzo Galluzzi
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  2. Guido Kroemer
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Correspondence to Lorenzo Galluzzi or Guido Kroemer.

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Competing interests

L.G. declares having held research contracts with Lytix Biopharma and Promontory, has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation, and holds Promontory stock options. G.K. declares having held research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sotio, Tollys, Vascage and Vasculox/Tioma, has received consulting/advisory honoraria from Reithera, is on the Board of Directors of the Bristol Myers Squibb Foundation France, is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio, and is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders, including patents licensed to Bayer (WO2014020041-A1, WO2014020043-A1), Bristol-Myers Squibb (WO2008057863-A1), Osasuna Therapeutics (WO2019057742A1), PharmaMar (WO2022048775-A1), Raptor Pharmaceuticals (EP2664326-A1), Samsara Therapeutics (GB202017553D0 and GB202017030D0), and Therafast Bio (EP3684471A1).

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Galluzzi, L., Kroemer, G. Immuno-epigenetic escape of cancer stem cells. Nat Immunol 23, 1300–1302 (2022). https://doi.org/10.1038/s41590-022-01293-0

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