Methods to Detect Immunogenic Cell Death In Vivo

  • Takahiro Yamazaki
  • Aitziber Buqué
  • Marissa Rybstein
  • Jonathan Chen
  • Ai Sato
  • Lorenzo GalluzziEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2055)


In response to selected stressors, cancer cells can undergo a form of regulated cell death that—in immunocompetent syngeneic hosts—is capable of eliciting an adaptive immune response specific for dead cell-associated antigens. Thus, such variant of regulated cell death manifests with robust antigenicity and adjuvanticity. As compared to their normal counterparts, malignant cells are highly antigenic per se, implying that they express a variety of antigens that are not covered by central tolerance. However, the precise modality through which cancer cells die in response to stress has a major influence on adjuvanticity. Moreover, the adjuvanticity threshold to productively drive anticancer immune responses is considerably lower in tumor-naïve hosts as compared to their tumor-bearing counterparts, largely reflecting the establishment of peripheral tolerance to malignant lesions in the latter (but not in the former). So far, no cellular biomarker or combination thereof has been found to reliably predict the ability of cancer cell death to initiate antitumor immunity. Thus, although some surrogate biomarkers of adjuvanticity can be used for screening purposes, the occurrence of bona fide immunogenic cell death (ICD) can only be ascertained in vivo. Here, we describe two methods that can be harnessed to straightforwardly determine the immunogenicity of mouse cancer cells succumbing to stress in both tumor-naïve and tumor-bearing hosts.

Key words

Abscopal effect Anthracycline-based chemotherapy CD8+ cytotoxic T lymphocytes Damage-associated molecular patterns Dendritic cells Radiation therapy Vaccination 



The authors are supported by a Breakthrough Level 2 grant from the US Department of Defense (DoD), Breast Cancer Research Program (BRCP) (#BC180476P1), by a startup grant from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, USA), by industrial collaborations with Lytix (Oslo, Norway) and Phosplatin (New York, USA), and by donations from Phosplatin (New York, USA), the Luke Heller TECPR2 Foundation (Boston, USA), and Sotio a.s. (Prague, Czech Republic).

Author Disclosure: L.G. provides remunerated consulting to OmniSEQ (Buffalo, NY, USA), Astra Zeneca (Gaithersburg, MD, USA), VL47 (New York, NY, USA), and the Luke Heller TECPR2 Foundation (Boston, MA, USA), and he is member of the Scientific Advisory Committee of OmniSEQ (Buffalo, NY, USA). The other authors have no conflicts of interest to disclose.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Takahiro Yamazaki
    • 1
  • Aitziber Buqué
    • 1
  • Marissa Rybstein
    • 1
  • Jonathan Chen
    • 1
  • Ai Sato
    • 1
  • Lorenzo Galluzzi
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Radiation OncologyWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Sandra and Edward Meyer Cancer CenterNew YorkUSA
  3. 3.Université Paris Descartes/Paris VParisFrance

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