Abstract
The efficacy of cancer therapies strongly relies on their ability to reinstate cancer immunosurveillance. Numerous biomedical approaches with immunotherapeutic activity have been developed to reeducate the host immune system to detect and clear tumor cells. Cytotoxicants have been primarily designed to slow down malignant cell proliferation and to induce programmed cell death. Some cytotoxic stimuli are able to activate a particular type of apoptosis, which is referred to as immunogenic cell death (ICD), that de facto convert cancer cells into their own vaccine. This effect ultimately facilitates the establishment of an antitumor immune response that potentially annihilates spared malignant cells, as well as an immune memory that prevents cancer recurrence. Based on the characteristic hallmarks of ICD, protocols have been developed to validate ICD induction in vitro, ex vivo, and in vivo. These methods may contribute to identify novel ICD inducers and to design multimodal regimens with superior therapeutic efficacy. Moreover, their translation into clinical research could have prognostic or predictive value. This chapter will introduce the “gold standard” protocol for the in vivo assessment of ICD in mice. The procedure relies on vaccination with treated cancer cells, followed by rechallenge with living entities of the same type, in syngeneic immunocompetent animals.
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Acknowledgments
The Kroemer lab 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). JH is the recipient of a PhD fellowship from the Swiss Fondation Philanthropia. SL is the recipient of a PhD fellowship from the French Ministry of Higher Education and Research.
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Humeau, J., Lévesque, S., Kroemer, G., Pol, J.G. (2019). Gold Standard Assessment of Immunogenic Cell Death in Oncological Mouse Models. In: López-Soto, A., Folgueras, A. (eds) Cancer Immunosurveillance. Methods in Molecular Biology, vol 1884. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8885-3_21
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