ArticleCancer research2022
Stress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Transcriptomic profiling of TSST-1-induced cytotoxicity and inflammatory responses in human vaginal epithelial cells.BMC microbiology · 2026Article
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- Immunometabolic Reprogramming of Fibroblastic Reticular Cells in the Tumor Immune Microenvironment.BioMed research international · 2026Review
- Integrating T cell signaling and metabolism to enhance T cell engager responses in solid tumors.Frontiers in immunology · 2026Review
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- The nonsteroidal anti-inflammatory drug sulindac reverses obesity-driven immunosuppression and triple-negative breast cancer progression.Breast cancer research : BCR · 2025Article
- Intra-tumoral hypoxia promotes CD8Immunity · 2025Article
- Faithful modeling of terminal CD8+T cell dysfunction and epigenetic stabilization in vitro.JCI insight · 2025Article
- Endoplasmic reticulum stress responses in anticancer immunity.Nature reviews. Cancer · 2025Review
- Blood-based transcriptomic biomarkers for response to [EJNMMI research · 2025Article
- Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.Journal of hematology & oncology · 2024Review
- ER-associated degradation adapter Sel1L is required for CD8Cell reports · 2024Article
- Acetyl-CoA carboxylase obstructs CD8Cell metabolism · 2024Article
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.Current cancer drug targets · 2024Review
- Unfolded protein responses in T cell immunity.Frontiers in immunology · 2024Review
- Development and validation of polyamines metabolism-associated gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma.Frontiers in immunology · 2023Article
- The ER-Mitochondria Interface as a Dynamic Hub for T Cell Efficacy in Solid Tumors.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2α (eukaryotic translation initiation factor 2 alpha). Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2α undermines the ability of T cells to suppress tumor growth. Reprograming T-cell metabolism was able to alleviate p-eIF2α accumulation and translational attenuation in the TME, allowing for sustained protein translation. Metabolic and pharmacological approaches showed that proteasome activity mitigates induction of p-eIF2α to support optimal antitumor T-cell function, protecting from translation attenuation and enabling prolonged cytokine synthesis in solid tumors. Together, these data identify a new therapeutic avenue to fuel the efficacy of tumor immunotherapy. SIGNIFICANCE: Proteasome function is a necessary cellular component for endowing T cells with tumor killing capacity by mitigating translation attenuation resulting from the unfolded protein response induced by stress in the tumor microenvironment.
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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.