Consensus guidelines for the detection of immunogenic cell death

The long-standing notion that apoptotic cells are unable to elicit an adaptive immune response has nowadays been refuted. Specific stimuli are indeed capable of eliciting a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system. We named such a variant of apoptosis, which is accompanied by the spatiotemporally defined emission of a panel of damage-associated molecular patterns, “immunogenic cell death” (ICD). Several chemotherapeutics that have been successfully employed in the clinic for decades 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 intrinsically incompatible with large screening campaigns. Here, we outline strategies for detecting surrogate markers of ICD in vitro and screening ample chemical libraries for putative ICD inducers using a high-content, high-throughput platform that we recently developed. This technology should facilitate the development of next-generation anticancer regimens, which simultaneously kill malignant cells as they convert them into a cancer-specific therapeutic vaccine.