期刊
IMMUNOLOGICAL REVIEWS
卷 280, 期 1, 页码 165-174出版社
WILEY
DOI: 10.1111/imr.12582
关键词
autophagy; calreticulin; endoplasmic reticulum stress; hyperploidy; immunopeptidome
类别
资金
- Institut Universitaire de France
- Ligue contre le Cancer
- Agence National de la Recherche
- Canceropole Ile-de-France
- Fondation pour la Recherche Medicale
- Institut National du Cancer
- LabEx Immuno-Oncology
- LeDucq Foundation
- Associazione Italiana per la Ricerca contro il Cancro [18418]
- Ministero Italiano della Salute [RF_GR-2013-02357273]
- Paris Alliance of Cancer Research Institutes (PACRI)
- Association pour la recherche sur le cancer [PJA20151203519]
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- RHU Torino Lumiere
- FP7 Ideas: European Research Council
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据