ArticleThe EMBO journal2025
Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hyperbaric oxygen therapy modulates immune effector responses and reshapes peripheral immune tolerance: a narrative review.Frontiers in immunology · 2026Pooled it
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- Review
- Review
- Prognostic Value of EEF1A1 and Its Correlation with Immune Regulation in Kidney Renal Clear Cell Carcinoma.Cancers · 2026Article
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Review
- From barrier to trigger: leveraging tumor hypoxia for precise control of CAR-T cell activity.Molecular biology reports · 2026Review
- Integrated hypoxia and metabolic gene signature to predict clinical outcomes and therapeutic vulnerabilities in lung adenocarcinoma.Journal of thoracic disease · 2026Article
- Iron-based magnetic nanoplatforms for immune microenvironment remodeling and cancer immunotherapy: progress and prospects.Journal of nanobiotechnology · 2026Review
- Article
- PSD3 links autophagic flux to MHC-I-associated immune modulation in esophageal squamous cell carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Review
- Modulation of the immunogenic landscape in colorectal cancer by mitochondrial methylation-controlled J protein.Molecular biomedicine · 2026Article
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.e., the immunopeptidome). Hypoxia decreases MHC-I expression in an oxygen-dependent manner, via activation of autophagy through the PERK arm of the unfolded protein response. Using an immunopeptidomics-based LC-MS approach, we find a significant reduction of presented antigens under hypoxia. Inhibition of autophagy under hypoxia enhances antigen presentation. In experimental tumors, reducing mitochondrial metabolism through a respiratory complex-I inhibitor increases tumor oxygenation, as well as MHC-I levels and the immunopeptidome. These data explain the molecular basis of tumor immune evasion in hypoxic conditions, and have implications for future therapeutic interventions targeting hypoxia-induced alterations in antigen presentation.
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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.