期刊
SEMINARS IN CANCER BIOLOGY
卷 33, 期 -, 页码 86-92出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2015.02.004
关键词
Apoptosis; ATF4; Autophagy; IRE1 alpha; PERK
类别
资金
- Ligue contre le Cancer (equipe labelisee)
- Agence National de la Recherche (ANR)
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- AXA Chair for Longevity Research
- Institut National du Cancer (INCa)
- Fondation Bettencourt-Schueller
- Fondation de France
- Fondation pour la Recherche Medicale (FRM)
- European Commission (ArtForce)
- European Research Council (ERC)
- LabEx Immuno-Oncology
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
Cancer cells exposed to some forms of chemotherapy and radiotherapy die while eliciting an adaptive immune response. Such a functionally peculiar variant of apoptosis has been dubbed immunogenic cell death (ICD). One of the central events in the course of ICD is the activation of an endoplasmic reticulum (ER) stress response. This is instrumental for cells undergoing ICD to emit all the signals that are required for their demise to be perceived as immunogenic by the host, and culminates with the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha). In particular, eIF2 alpha phosphorylation is required for the pre-apoptotic exposure of the ER chaperone calreticulin (CALR) on the cell surface, which is a central determinant of ICD. Importantly, phosphoiylated eIF2a can be quantified in both preclinical and clinical samples by immunoblotting or immunohistochemistry using phosphoneoepitope-specific monoclonal antibodies. Of note, the phosphorylation of eIF2 alpha and CALR exposure do not necessarily correlate with each other, and neither of these parameters is sufficient for cell death to be perceived as immunogenic. Nonetheless, accumulating data indicate that assessing the degree of phosphorylation of eIF2 alpha provides a convenient parameter to monitor ICD. Here, we discuss the role of the ER stress response in ICD and the potential value of eIF2 alpha phosphorylation as a biomarker for this clinically relevant variant of apoptosis. (C) 2015 Elsevier Ltd. All rights reserved.
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