Cancer and Metastasis Reviews

, Volume 30, Issue 1, pp 61–69 | Cite as

Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy

  • Oliver Kepp
  • Lorenzo Galluzzi
  • Isabelle Martins
  • Frederic Schlemmer
  • Sandy Adjemian
  • Mickael Michaud
  • Abdul Qader Sukkurwala
  • Laurie Menger
  • Laurence Zitvogel
  • Guido KroemerEmail author


The success of some chemo- and radiotherapeutic regimens relies on the induction of immunogenic tumor cell death and on the induction of an anticancer immune response. Cells succumbing to immunogenic cell death undergo specific changes in their surface characteristics and release pro-immunogenic factors according to a defined spatiotemporal pattern. This stimulates antigen presenting cells such as dendritic cells to efficiently take up tumor antigens, process them, and cross-prime cytotoxic T lymphocytes, thus eliciting a tumor-specific cognate immune response. Such a response can also target therapy-resistant tumor (stem) cells, thereby leading, at least in some instances, to tumor eradication. In this review, we shed some light on the molecular identity of the factors that are required for cell death to be perceived as immunogenic. We discuss the intriguing observations that the most abundant endoplasmic reticulum protein, calreticulin, the most abundant intracellular metabolite, ATP, and the most abundant non-histone chromatin-binding protein, HMGB1, can determine whether cell death is immunogenic as they appear on the surface or in the microenvironment of dying cells.


Apoptosis ATP Calreticulin HMGB1 Necrosis Spatiotemporal codes 



Antigen presenting cell




Danger-associated molecular pattern


Dendritic cell


Eukaryotic translation initiation factor 2α


eIF2α kinase 3


Endoplasmic reticulum


Ectonucleoside triphosphate diphosphohydrolase




High-mobility group box 1


Heat shock protein


Immunogenic cell death








Major histocompatibility complex


Myeloid differentiation primary response protein 88


NLR family, pyrin domain containing 3


Nitric oxide


Oxidized low-density lipoproteins


Pathogen-associated molecular pattern




PYD and CARD domain containing


RNA interference


Signal-regulatory protein α


SNAP and NSF attachment receptors


S-nitroso-l-cysteine ethyl esther


Surfactant protein A


Toll-like receptor


Wild type



GK is supported by the Ligue Nationale contre le Cancer (Equipes labellisée), Agence Nationale pour la Recherche (ANR), European Commission (Apo-Sys, ChemoRes, ApopTrain), Fondation pour la Recherche Médicale (FRM), Institut National du Cancer (INCa), and Cancéropôle Ile-de-France. IM is supported by the Ligue Nationale contre le Cancer, OK by AICR, LG by Apo-Sys and FS by FRM.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Oliver Kepp
    • 1
    • 2
    • 3
  • Lorenzo Galluzzi
    • 1
    • 2
    • 3
  • Isabelle Martins
    • 1
    • 2
    • 3
  • Frederic Schlemmer
    • 1
    • 2
    • 3
  • Sandy Adjemian
    • 1
    • 2
    • 3
  • Mickael Michaud
    • 1
    • 2
    • 3
  • Abdul Qader Sukkurwala
    • 1
    • 2
    • 3
  • Laurie Menger
    • 1
    • 2
    • 3
  • Laurence Zitvogel
    • 2
    • 3
    • 4
  • Guido Kroemer
    • 1
    • 5
    • 6
    • 7
    • 8
    Email author
  1. 1.INSERM, U848, Institut Gustave Roussy, Pavillon de Recherche 1Villejuif (Paris)France
  2. 2.Institut Gustave RoussyVillejuifFrance
  3. 3.Université Paris Sud, Paris 11VillejuifFrance
  4. 4.INSERM, U1015, and CICBT507VillejuifFrance
  5. 5.Metabolomics Platform, Institut Gustave RoussyVillejuifFrance
  6. 6.Centre de Recherche des CordeliersParisFrance
  7. 7.Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HPParisFrance
  8. 8.Université Paris Descartes, Paris 5ParisFrance

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