Immunogenic cell death in cancer therapy: Present and emerging inducers

J Cell Mol Med. 2019 Aug;23(8):4854-4865. doi: 10.1111/jcmm.14356. Epub 2019 Jun 18.

Abstract

In the tumour microenvironment (TME), immunogenic cell death (ICD) plays a major role in stimulating the dysfunctional antitumour immune system. Chronic exposure of damage-associated molecular patterns (DAMPs) attracts receptors and ligands on dendritic cells (DCs) and activates immature DCs to transition to a mature phenotype, which promotes the processing of phagocytic cargo in DCs and accelerates the engulfment of antigenic components by DCs. Consequently, via antigen presentation, DCs stimulate specific T cell responses that kill more cancer cells. The induction of ICD eventually results in long-lasting protective antitumour immunity. Through the exploration of ICD inducers, recent studies have shown that there are many novel modalities with the ability to induce immunogenic cancer cell death. In this review, we mainly discussed and summarized the emerging methods for inducing immunogenic cancer cell death. Concepts and molecular mechanisms relevant to antitumour effects of ICD are also briefly discussed.

Keywords: ICD inducers; antitumour effects; damage-associated molecular patterns; dendritic cells; immune system; immunogenic cancer cell death.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Endoplasmic Reticulum Stress / immunology
  • Humans
  • Immunogenic Cell Death / genetics*
  • Immunotherapy
  • Mitochondrial Membranes / immunology
  • Mitochondrial Membranes / metabolism
  • Nanoparticles / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Phototherapy
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents
  • Calreticulin