Danger signalling during cancer cell death: origins, plasticity and regulation

Cell Death Differ. 2014 Jan;21(1):26-38. doi: 10.1038/cdd.2013.48. Epub 2013 May 17.


Accumulating data indicates that following anti-cancer treatments, cancer cell death can be perceived as immunogenic or tolerogenic by the immune system. The former is made possible due to the ability of certain anti-cancer modalities to induce immunogenic cell death (ICD) that is associated with the emission of damage-associated molecular patterns (DAMPs), which assist in unlocking a sequence of events leading to the development of anti-tumour immunity. In response to ICD inducers, activation of endoplasmic reticulum (ER) stress has been identified to be indispensable to confer the immunogenic character of cancer cell death, due to its ability to coordinate the danger signalling pathways responsible for the trafficking of vital DAMPs and subsequent anti-cancer immune responses. However, in recent times, certain processes apart from ER stress have emerged (e.g., autophagy and possibly viral response-like signature), which have the ability to influence danger signalling. In this review, we discuss the molecular nature, emerging plasticity in the danger signalling mechanisms and immunological impact of known DAMPs in the context of immunogenic cancer cell death. We also discuss key effector mechanisms modulating the interface between dying cancer cells and the immune cells, which we believe are crucial for the therapeutic relevance of ICD in the context of human cancers, and also discuss the influence of experimental conditions and animal models on these.

Publication types

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

MeSH terms

  • Animals
  • Cell Death* / immunology
  • Cytokines / metabolism
  • Endoplasmic Reticulum Stress
  • Humans
  • Immune System / metabolism
  • Molecular Chaperones / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*
  • T-Lymphocytes / immunology


  • Cytokines
  • Molecular Chaperones
  • Reactive Oxygen Species