Molecular characteristics of immunogenic cancer cell death

Cell Death Differ. 2008 Jan;15(1):3-12. doi: 10.1038/sj.cdd.4402269. Epub 2007 Nov 16.


Apoptotic cell death is initiated by a morphologically homogenous entity that was considered to be non-immunogenic and non-inflammatory in nature. However, recent advances suggest that apoptosis, under certain circumstances, can be immunogenic. In particular, some characteristics of the plasma membrane, acquired at preapoptotic stage, can cause immune effectors to recognize and attack preapoptotic tumor cells. The signals that mediate the immunogenicity of tumor cells involve elements of the DNA damage response (such as ataxia telangiectasia mutated and p53 activation), elements of the endoplasmic reticulum stress response (such as eukaryotic initiation factor 2alpha phosphorylation), as well as elements of the apoptotic response (such as caspase activation). Depending on the signal-transduction pathway, tumor cells responding to chemotherapy or radiotherapy can express 'danger' and 'eat me' signals on the cell surface (such as NKG2D ligands, heat-shock proteins and calreticulin) or can secrete/release immunostimulatory factors (such as cytokines and high-mobility group box 1) to stimulate innate immune effectors. Likewise, the precise sequence of such events influences the 'decision' of the immune system to mount a cognate response or not. We therefore anticipate that the comprehension of the mechanisms governing the immunogenicity of cell death will have a profound impact on the design of anticancer therapies.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Autophagy
  • Calreticulin / metabolism
  • Cell Death / immunology*
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • HMGB1 Protein / immunology
  • HMGB1 Protein / metabolism
  • Heat-Shock Proteins / immunology
  • Heat-Shock Proteins / metabolism
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Killer Cells, Natural / immunology
  • Necrosis
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Phagocytosis
  • T-Lymphocytes / immunology
  • Tumor Suppressor Protein p53 / metabolism


  • Calreticulin
  • Cytokines
  • HMGB1 Protein
  • Heat-Shock Proteins
  • Inflammation Mediators
  • Tumor Suppressor Protein p53