ArticleCell death and differentiation2018
eIF2α phosphorylation is pathognomonic for immunogenic cell death.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Pooled it
- Sequential versus concurrent neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma: a randomized, controlled, open-label, phase 2 trial (HCHTOG1906).Frontiers in immunology · 2026Trial
- KRAS-elicited PDIA6 blocks PERK-dependent immunogenic cell death in pancreatic carcinoma.Oncoimmunology · 2026Article
- STAT3 inhibition for the induction of immunogenic cell death in multiple myeloma.Oncoimmunology · 2026Article
- A chemical-genetic system for calreticulin exposure on cancer cells reveals immune-dependent antitumor effects.Cell death and differentiation · 2026Article
- Spatiotemporally Controlled Sequential Chemo-Immunotherapy Activates Pyroptosis for Robust Anti-Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond the barrier: Engineering the tumor-immune-soil nexus-a mechanistic blueprint for integrating Traditional Chinese Medicine with immunotherapy in metastatic colorectal cancer.Medical oncology (Northwood, London, England) · 2026Review
- Calreticulin as a stress-responsive integrator of ER proteostasis, calcium homeostasis, and immune clearance.Molecular biology reports · 2026Review
- Nanoplatforms for EGFR-TKI resistance reversion and immunoactivation in NSCLC by ER stress and siRNA intervention.Journal of nanobiotechnology · 2026Article
- Review
- Chimeric biohybrid nanovesicles induce immunogenic cell death for targeted and immune-potentiated glioblastoma therapy.Asian journal of pharmaceutical sciences · 2026Article
- Trifluridine/tipiracil enhances radiation-induced abscopal effects and augments PD-1 blockade in gastric cancer.Scientific reports · 2026Article
- The Role of Stress Granules in Cardiovascular Diseases.Reviews in cardiovascular medicine · 2026Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor-Associated Macrophage-Mediated Prostate Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Organoplatinum(II) Type II Immunogenic Cell Death Inducers Target Protein Tyrosine Phosphatase 1B to Drive Immunogenicity.Journal of the American Chemical Society · 2026Article
- Binary mineral nanoparticles enable intravascular delivery of metal ions to tumors for metalloimmunotherapy.Nature communications · 2026Article
- Microenvironment-defined priority pathways shape ICD-driven abscopal responses.Frontiers in immunology · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Simultaneous induction of immunogenic cell death and PD-L1 downregulation by bufalin-based nanovaccines for potentiate HCC immunotherapy.Materials today. Bio · 2025Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphorylation of eIF2α is essential for the endoplasmic reticulum (ER) stress response, the formation of stress granules, as well as macroautophagy. Several successful anticancer chemotherapeutics have the property to induce immunogenic cell death (ICD), thereby causing anticancer immune responses. ICD is accompanied by the translocation of calreticulin (CALR) from the ER lumen to the plasma membrane, which facilitates the transfer of tumor-associated antigens to dendritic cells. Here we systematically investigated the capacity of anticancer chemotherapeutics to induce signs of ER stress. ICD inducers including anthracyclines and agents that provoke tetraploidization were highly efficient in enhancing the phosphorylation of eIF2α, yet failed to stimulate other signs of ER stress including the transcriptional activation of activating transcription factor 4 (ATF4), the alternative splicing of X-box binding protein 1 (XBP1s) mRNA and the proteolytic cleavage of activating transcription factor 6 (ATF6) both in vitro and in cancers established in mice. Systematic analyses of clinically used anticancer chemotherapeutics revealed that only eIF2α phosphorylation, but none of the other signs of ER stress, correlated with CALR exposure. eIF2α phosphorylation induced by mitoxantrone, a prototype ICD-inducing anthracyline, was mediated by eIF2α kinase-3 (EIF2AK3). Machine-learning approaches were used to determine the physicochemical properties of drugs that induce ICD, revealing that the sole ER stress response relevant to the algorithm is eIF2α phosphorylation with its downstream consequences CALR exposure, stress granule formation and autophagy induction. Importantly, this approach could reduce the complexity of compound libraries to identify ICD inducers based on their physicochemical and structural characteristics. In summary, it appears that eIF2α phosphorylation constitutes a pathognomonic characteristic of ICD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.