Trial watch: chemotherapy-induced immunogenic cell death in oncology

Abstract

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.

Keywords: CAR T cells, antigen-presenting cells; chemotherapy; danger signals; dendritic cell; immune-checkpoint blockers; immunogenic cell death; immunotherapy.

Figure 1.

Recently published clinical studies testing immunogenic cell death (ICD)-inducing chemotherapy in oncology that investigate the immunogenic response. Clinical studies were classified on: (a) cancer type, (b) ICD-inducing drug, (c) combinatorial immunotherapy. (d) immunomonitoring approach, CAR, chimeric antigen receptor; CRC, colorectal carcinoma; ICB, immune checkpoint blocker; IHC, immunohistochemistry; PD-L1, programmed death-ligand; TIL, tumor-infiltrating lymphocyte.