ArticleOncotarget2014
Elevated endoplasmic reticulum stress reinforced immunosuppression in the tumor microenvironment via myeloid-derived suppressor cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 100 citations in OpenAlex.
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Exosomes Derived from Endoplasmic Reticulum Stressed Hepatocellular Carcinoma Cells Enhance the Antitumor Immunity of Dendritic Cells.Inflammation · 2025Article
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- Article
- Key players of immunosuppression in epithelial malignancies: Tumor-infiltrating myeloid cells and γδ T cells.Cancer reports (Hoboken, N.J.) · 2024Review
- Schisandrin B Suppresses Colon Cancer Growth by Inducing Cell Cycle Arrest and Apoptosis: Molecular Mechanism and Therapeutic Potential.ACS pharmacology & translational science · 2024Article
- The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma.Discover oncology · 2024Article
- Immune cell networking in solid tumors: focus on macrophages and neutrophils.Frontiers in immunology · 2024Review
- Cholesterol induction in CD8Cancer immunology, immunotherapy : CII · 2023Article
- METTL3-mediated m6A methylation regulates ovarian cancer progression by recruiting myeloid-derived suppressor cells.Cell & bioscience · 2023Article
- An endoplasmic reticulum stress-related signature could robustly predict prognosis and closely associate with response to immunotherapy in pancreatic ductal adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Article
- Modulation of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment by Natural Products.Archivum immunologiae et therapiae experimentalis · 2023Review
- Article
- Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis.BMC pulmonary medicine · 2023Article
- Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment.Molecular cancer research : MCR · 2023Article
- Endoplasmic reticulum stress mediates the myeloid-derived immune suppression associated with cancer and infectious disease.Journal of translational medicine · 2023Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of endoplasmic reticulum (ER) stress in cancer has been studied in detail, and ER stress is known to increase tumor cell apoptosis, and thus, reduce tumor growth. However, in our study, persistent ER stress induced by multiple administrations of low-dose thapsigargin (Tg) accelerated tumor growth in mice. Tg-mediated ER stress increased the generation of Ly6G+CD11b+ myeloid cells, but did not alter anti-tumor effector T cells. 4-Phenylbutyric acid (4-PBA), a chemical chaperone widely used as an ER stress reducer, attenuated Tg-induced myeloid-derived suppressor cell (MDSC) expansion and tumor growth. Tg-mediated ER stress enhanced the immunosuppressive capacity of tumor-infiltrating MDSCs by increasing expression of ARG1, iNOS, and NOX2, although splenic MDSCs were not affected. Consistent with these results, 4-PBA restored the anti-tumor immune response by regulating inflammatory cytokines such as TNF-α and CXCL1/KC, and activated tumor-infiltrating CD8+ T cells that were inhibited by Tg-mediated ER stress. These results suggest that significant ER stress in a tumor-bearing host might induce tumor growth mediated by enhancement of MDSC-mediated suppression. Therefore, ER stress reducers such as 4-PBA could restore anti-tumor immunity by inhibiting suppressive MDSCs that are exacerbated by ER stress.
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Registered trials
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.