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Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy

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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.

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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

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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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Authors and Affiliations

  1. INSERM, U848, Institut Gustave Roussy, Pavillon de Recherche 1, 94805, Villejuif (Paris), France

    Oliver Kepp, Lorenzo Galluzzi, Isabelle Martins, Frederic Schlemmer, Sandy Adjemian, Mickael Michaud, Abdul Qader Sukkurwala, Laurie Menger & Guido Kroemer

  2. Institut Gustave Roussy, 94805, Villejuif, France

    Oliver Kepp, Lorenzo Galluzzi, Isabelle Martins, Frederic Schlemmer, Sandy Adjemian, Mickael Michaud, Abdul Qader Sukkurwala, Laurie Menger & Laurence Zitvogel

  3. Université Paris Sud, Paris 11, 94805, Villejuif, France

    Oliver Kepp, Lorenzo Galluzzi, Isabelle Martins, Frederic Schlemmer, Sandy Adjemian, Mickael Michaud, Abdul Qader Sukkurwala, Laurie Menger & Laurence Zitvogel

  4. INSERM, U1015, and CICBT507, 94805, Villejuif, France

    Laurence Zitvogel

  5. Metabolomics Platform, Institut Gustave Roussy, 94805, Villejuif, France

    Guido Kroemer

  6. Centre de Recherche des Cordeliers, 75005, Paris, France

    Guido Kroemer

  7. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75908, Paris, France

    Guido Kroemer

  8. Université Paris Descartes, Paris 5, 75270, Paris, France

    Guido Kroemer

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  1. Oliver Kepp
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  2. Lorenzo Galluzzi
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Correspondence to Guido Kroemer.

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Oliver Kepp and Lorenzo Galluzzi contributed equally to this work.

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Kepp, O., Galluzzi, L., Martins, I. et al. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 30, 61–69 (2011). https://doi.org/10.1007/s10555-011-9273-4

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