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 Kroemer
Article

Abstract

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.

Keywords

Apoptosis ATP Calreticulin HMGB1 Necrosis Spatiotemporal codes 

Abbreviations

APC

Antigen presenting cell

CRT

Calreticulin

DAMP

Danger-associated molecular pattern

DC

Dendritic cell

eIF2α

Eukaryotic translation initiation factor 2α

EIF2AK3

eIF2α kinase 3

ER

Endoplasmic reticulum

ENTPD1

Ectonucleoside triphosphate diphosphohydrolase

Gb3

Globotriaosylceramide

HMGB1

High-mobility group box 1

HSP

Heat shock protein

ICD

Immunogenic cell death

IFN-γ

Interferon-γ

IL-1β

Interleukin-1β

LPS

Lipopolysaccharide

MHC

Major histocompatibility complex

MYD88

Myeloid differentiation primary response protein 88

NLRP3

NLR family, pyrin domain containing 3

NO

Nitric oxide

oxLDLs

Oxidized low-density lipoproteins

PAMP

Pathogen-associated molecular pattern

PS

Phosphatidylserine

PYCARD

PYD and CARD domain containing

RNAi

RNA interference

SIRPα

Signal-regulatory protein α

SNARE

SNAP and NSF attachment receptors

SNCEE

S-nitroso-l-cysteine ethyl esther

SPA

Surfactant protein A

TLR

Toll-like receptor

WT

Wild type

Notes

Acknowledgments

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
  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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