Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy

Abstract

Immunogenic cell death (ICD), which is triggered by exposure of tumor cells to a limited range of anticancer drugs, radiotherapy, and photodynamic therapy, represents a recent innovation in the revitalized and burgeoning field of oncoimmunnotherapy. ICD results in the cellular redistribution and extracellular release of damage-associated molecular patterns (DAMPs), which have the potential to activate and restore tumor-targeted immune responses. Although a convincing body of evidence exists with respect to the antitumor efficacy of ICD in various experimental systems, especially murine models of experimental anticancer immunotherapy, evidence for the existence of ICD in the clinical setting is less compelling. Following overviews of hallmark developments, which have sparked the revival of interest in the field of oncoimmunotherapy, types of tumor cell death and the various DAMPs most prominently involved in the activation of antitumor immune responses, the remainder of this review is focused on strategies which may potentiate ICD in the clinical setting. These include identification of tumor- and host-related factors predictive of the efficacy of ICD, the clinical utility of combinatorial immunotherapeutic strategies, novel small molecule inducers of ICD, novel and repurposed small molecule immunostimulants, as well as the critical requirement for validated biomarkers in predicting the efficacy of ICD.