Trial watch: chemotherapy-induced immunogenic cell death in oncology

Oncoimmunology. 2023 Jun 3;12(1):2219591. doi: 10.1080/2162402X.2023.2219591. eCollection 2023.

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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Death
  • Cytokines / metabolism
  • Humans
  • Immunogenic Cell Death
  • Neoplasms*

Substances

  • Antineoplastic Agents
  • Cytokines

Grants and funding

This study is supported by Research Foundation Flanders (FWO) (Fundamental Research Grant, G0B4620N to ADG; Excellence of Science/EOS grant, 30837538, for ‘DECODE’ consortium, for ADG), KU Leuven (C1 grant, C14/19/098; C3 grant, C3/21/037; and POR award funds, POR/16/040 to ADG), Kom op Tegen Kanker (KOTK/2018/11509/1 and KOTK/2019/11955/1 to ADG) and VLIR-UOS (iBOF grant, iBOF/21/048, for ‘MIMICRY’ consortium to ADG and ST). IV and RSL are supported by FWO-SB PhD Fellowship (1S06821N and 1S44123N). JS is funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society through the Emmanuel van der Schueren (EvDS) PhD fellowship (projectID: 12699). DMB got support from Senior Postdoctoral FWO fellowship (1279223N) and KU Leuven’s Postdoctoral mandate grant (PDMT1/21/032).