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Immunogenicity of necrotic cell death

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Abstract

The mode of tumor cell death has significant effects on anti-tumor immunity. Although, previously it was thought that cell death is an inert effect, different investigators have clearly shown that dying tumors can attract, activate and mature professional antigen presenting cells and dendritic cells. In addition, others and we have shown that the type of tumor cell death not only controls the presence or absence of specific tumor antigens, but also can result in immunological responses ranging from immunosuppression to anti-tumor immunity. More importantly, it is possible to enhance anti-tumor immunity both in vitro and in vivo by targeting specific molecular mechanisms such as oligopeptidases and the proteasome. These studies not only extend our knowledge on basic immunological questions and the induction of anti-tumor immunity, but also have implications for all types of cancer treatments, in which rapid tumor cell death is induced. This review is a comprehensive summary of cell death and particularly necrosis and the pivotal role it plays in anti-tumor immunity.

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Abbreviations

DAMP:

Damage-associated molecular pattern molecules

PAMP:

Pathogen-associated molecular pattern molecules

IFN:

Interferon

HMGB1:

High mobility group box 1 protein

TNF:

Tumor necrosis factor

TLR:

Toll-like receptor

RIPK:

Receptor-interacting protein kinase

APC:

Antigen presenting cell

ICD:

Immunogenic cell death

ER:

Endoplasmic reticulum

ROS:

Reactive oxygen species

CRT:

Calreticulin

HSP:

Heat shock protein

LPS:

Lipopolysaccharide

RAGE:

Receptor for advanced glycosylation end product

IL:

Interleukin

RNP:

Ribonucleoproteins

PRR:

Pattern recognition receptor

DC:

Dendritic cell

DRiP:

Defective ribosomal product

OVA:

Ovalbumin

LAP:

Leuzin aminopeptidase

PSA:

Puromycine-sensitive aminopeptidase

BH:

Bleomycin hydrolase

TOP-1:

Thimet oligopeptidase 1

TPPII:

Tripeptidyl peptidase II

ERAP:

ER aminopeptidase

ERAAP:

ER aminopeptidase associated with antigen processing

DRibbles:

DRiPs-containing blebs

DPP-3:

Dipeptidyl peptidase 3

PEP:

Prolyl endopeptidase

Ag:

Antigen

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Acknowledgments

This work was supported by the Intramural Research Program of the NCI, NIH.

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Authors and Affiliations

  1. Department of Nephrology, Medizinische Hochschule Hannover, Hannover, Germany

    Jaba Gamrekelashvili

  2. Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH/NCI/CCR Building 10 Rm 12N226, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Tim F. Greten & Firouzeh Korangy

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  1. Jaba Gamrekelashvili
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Correspondence to Tim F. Greten.

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Gamrekelashvili, J., Greten, T.F. & Korangy, F. Immunogenicity of necrotic cell death. Cell. Mol. Life Sci. 72, 273–283 (2015). https://doi.org/10.1007/s00018-014-1741-x

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