Immunogenic Cell Death Driven by Radiation—Impact on the Tumor Microenvironment

  • Takahiro Yamazaki
  • Claire Vanpouille-Box
  • Sandra Demaria
  • Lorenzo GalluzziEmail author
Part of the Cancer Treatment and Research book series (CTAR, volume 180)


Immunogenic cell death (ICD) is a particular form of cell death that can initiate adaptive immunity against antigens expressed by dying cells in the absence of exogenous adjuvants. This implies that cells undergoing ICD not only express antigens that are not covered by thymic tolerance, but also deliver adjuvant-like signals that enable the recruitment and maturation of antigen-presenting cells toward an immunostimulatory phenotype, culminating with robust cross-priming of antigen-specific CD8+ T cells. Such damage-associated molecular patterns (DAMPs), which encompass cellular proteins, small metabolites and cytokines, are emitted in a spatiotemporally defined manner in the context of failing adaptation to stress. Radiation therapy (RT) is a bona fide inducer of ICD, at least when employed according to specific doses and fractionation schedules. Here, we discuss the mechanisms whereby DAMPs emitted by cancer cells undergoing RT-driven ICD alter the functional configuration of the tumor microenvironment.


Antigen cross-presentation ATP Autophagy CALR HGMB1 Type I interferon 



SD is supported by NCI R01CA198533 and R01CA201246, and by grants from the Breast Cancer Research Foundation and The Chemotherapy Foundation. LG lab is supported by a Breakthrough Level 2 grant from the US Department of Defense (DoD), Breast Cancer Research Program (BRCP) (#BC180476P1), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a startup grant from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by industrial collaborations with Lytix (Oslo, Norway) and Phosplatin (New York, US), and by donations from Phosplatin (New York, US), the Luke Heller TECPR2 Foundation (Boston, US) and Sotio a.s. (Prague, Czech Republic).

Conflict of Interest Statement.

TY and CVB have no relevant conflicts of interest to disclose. SD has research funding from Lytix Biopharma and Nanobiotix, is a member of the Scientific Advisory Board of Lytix Biopharma, and has received honorarium for consulting from EMD Serono and Mersana Therapeutics. LG received consulting fees from OmniSEQ, Astra Zeneca, Inzen and the Luke Heller TECPR2 Foundation, and he is member of the Scientific Advisory Committee of Boehringer Ingelheim, The Longevity Labs and OmniSEQ.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Takahiro Yamazaki
    • 1
  • Claire Vanpouille-Box
    • 1
    • 2
  • Sandra Demaria
    • 1
    • 2
  • Lorenzo Galluzzi
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of Radiation OncologyWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Sandra and Edward Meyer Cancer CenterNew YorkUSA
  3. 3.Caryl and Israel Englander Institute for Precision MedicineNew YorkUSA
  4. 4.Department of DermatologyYale School of MedicineNew HavenUSA
  5. 5.Université de ParisParisFrance

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