Immunogenic cell death and DAMPs in cancer therapy

Nat Rev Cancer. 2012 Dec;12(12):860-75. doi: 10.1038/nrc3380. Epub 2012 Nov 15.


Although it was thought that apoptotic cells, when rapidly phagocytosed, underwent a silent death that did not trigger an immune response, in recent years a new concept of immunogenic cell death (ICD) has emerged. The immunogenic characteristics of ICD are mainly mediated by damage-associated molecular patterns (DAMPs), which include surface-exposed calreticulin (CRT), secreted ATP and released high mobility group protein B1 (HMGB1). Most DAMPs can be recognized by pattern recognition receptors (PRRs). In this Review, we discuss the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Calreticulin / metabolism
  • Cell Death / immunology
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • HMGB1 Protein / immunology
  • HMGB1 Protein / metabolism
  • Humans
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • Neoplasms / therapy*
  • Phagocytosis / immunology
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism


  • Antineoplastic Agents
  • Calreticulin
  • HMGB1 Protein
  • Reactive Oxygen Species
  • Adenosine Triphosphate