Consensus guidelines for the detection of immunogenic cell death

By Oliver Kepp, L. Senovilla, Ilio Vitale, Erika Vacchelli, Sandy Adjemian, P. Agostinis, L. Apetoh, Fernando Aranda, V. Barnaba, N. Bloy and 72 more. Oncoimmunology, 2014

787 citations recorded by the source corpus.

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named “immunogenic cell death” (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Subfields: Epidemiology, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/95713f5eb93096833568c7a7419e88c8777917c7

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Citations in the corpus

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “Immunogenic cell death (ICD) is a functionally peculiar form of RCD that is sufficient to activate an adaptive immune response specific for endogenous (cellular) or exogenous (viral) antigens expressed by dying cells [852, 853].”
Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? (2018, background): “, 2016) or in a regulated fashion by immunogenic cell death, also called immunogenic apoptosis (Kepp et al., 2014; Garg et al., 2015a).”
Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. (2015, background): “Accordingly, cancer cells exposed to a lethal dose of anthracyclines in vitro and then inoculated into immunocompetent mice in the absence of adjuvants efficiently protect the animals from a subsequent challenge with living neoplastic cells of the same type (Kepp et al., 2014).”