Format

Send to

Choose Destination
Immunol Rev. 2017 Nov;280(1):165-174. doi: 10.1111/imr.12582.

Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance.

Bloy N1,2,3,4,5,6,7, Garcia P3,6,7, Laumont CM8,9, Pitt JM1,10,11, Sistigu A12, Stoll G1,2,3,4, Yamazaki T11, Bonneil E8, Buqué A1,2,3,4,6, Humeau J1,2,3,4,5,6,7, Drijfhout JW13,14, Meurice G15, Walter S16, Fritsche J17, Weinschenk T16,17, Rammensee HG18, Melief C19, Thibault P8,20, Perreault C8,9,21, Pol J1,2,3,4,6, Zitvogel L10,11,10, Senovilla L1,2,3,4, Kroemer G1,2,3,4,5,22,23.

Author information

1
Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
2
Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
3
Institut National de la Santé et de la Recherche Médicale, U1138, Paris, France.
4
Université Pierre et Marie Curie, Paris, France.
5
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
6
Institut Gustave Roussy Cancer Campus, Villejuif, France.
7
Faculty of Medicine, University of Paris Sud, Kremlin-Bicêtre, France.
8
Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada.
9
Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
10
Center of Clinical Investigations in Biotherapies of Cancer (CICBT), Villejuif, France.
11
Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Equipe Labellisée Ligue Nationale Contre le Cancer, Gustave Roussy Cancer Campus, Villejuif, France.
12
Unit of Tumor Immunology and Immunotherapy, Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy.
13
Department of Immunohematology and Blood Transfusion, Leiden University, Leiden, The Netherlands.
14
Medical Center, Leiden, The Netherlands.
15
Bioinformatic Core Facility, UMS AMMICA, INSERM US23, CNRS UMS3665, Gustave Roussy, Villejuif, France.
16
Immatics US, Houston, TX, USA.
17
Immatics Biotechnologies, Tübingen, Germany.
18
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
19
ISA Pharmaceuticals, Leiden, The Netherlands.
20
Department of Chemistry, Faculty of Arts and Sciences, Université de Montréal, Montreal, Quebec, Canada.
21
Division of Hematology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
22
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
23
Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the "eat-me" signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells. Hence, both autophagy and polyploidization cause the emission of adjuvant signals that ultimately elicit immune control by CD8+ T lymphocytes. We investigated the possibility that autophagy and polyploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. Mass spectrometry led to the identification of peptides that were presented on major histocompatibility complex (MHC) class I molecules in an autophagy-dependent fashion or that were specifically exposed on the surface of polyploid cells, yet lost upon passage of such cells through immunocompetent (but not immunodeficient) mice. However, the preferential recognition of autophagy-competent and polyploid cells by the innate and cellular immune systems did not correlate with the preferential recognition of such peptides in vivo. Moreover, vaccination with such peptides was unable to elicit tumor growth-inhibitory responses in vivo. We conclude that autophagy and polyploidy increase the immunogenicity of cancer cells mostly by affecting their adjuvanticity rather than their antigenicity.

KEYWORDS:

autophagy; calreticulin; endoplasmic reticulum stress; hyperploidy; immunopeptidome

PMID:
29027230
DOI:
10.1111/imr.12582
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center