ArticlePloS one2017
Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 117 citations in OpenAlex.
- Interactions Between Circulating Tumor Cells and the Immune System in Colorectal Cancer: Friends or Foes?Cancers · 2026Review
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges.Clinical and experimental immunology · 2026Review
- Immunogenicity remodeling in hepatocellular carcinoma: mechanisms and translational strategies.Therapeutic advances in medical oncology · 2026Review
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Hypoxia induced VEGF secretion promotes resistance to bispecific T-cell engagers.Signal transduction and targeted therapy · 2025Article
- Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.Cancer biology & therapy · 2025Article
- Review
- From Hypoxia to Bone: Reprogramming the Prostate Cancer Metastatic Cascade.International journal of molecular sciences · 2025Review
- Use of Radiomics in Characterizing Tumor Hypoxia.International journal of molecular sciences · 2025Review
- Tumor Hypoxia: How Conventional Histology Is Reshaped in Breast Carcinoma.International journal of molecular sciences · 2025Review
- Hypoxic tumor cell line lysate-pulsed dendritic cell vaccine exhibits better therapeutic effects on hepatocellular carcinoma.British journal of cancer · 2025Article
- Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia-induced immunosuppression.JCI insight · 2025Article
- Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.The EMBO journal · 2025Article
- Advances in the study of reversing tumor drug resistance by targeting cancer-associated fibroblasts with nanomaterials.Frontiers in immunology · 2025Review
- Therapeutic advantage of combinatorial chimeric antigen receptor T cell and chemotherapies.Pharmacological reviews · 2025Review
- RNA-seq analysis of blood from cave- and surface-dwellingFrontiers in physiology · 2025Article
- Hypoxic link between cancer cells and the immune system: The role of adenosine and lactate.Oncology research · 2025Review
- Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition.Frontiers in oncology · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF. In addition, hypoxia downregulated antigen presenting proteins like TAP 1/2 and LMP7 that are known to have a dominant role in surface display of peptide-MHC complexes. Corroborating oxygen-dependent regulation of MHC antigen presentation, hyperoxia (60% oxygen) transcriptionally upregulated MHC expression and increased levels of TAP2, LMP2 and 7. In conclusion, this study reveals a novel mechanism by which intra-tumoral hypoxia and HIF can potentiate immune escape. It also suggests the use of hyperoxia to improve tumor cell-based cancer vaccines and for mining novel immune epitopes. Furthermore, this study highlights the advantage of 3D cell cultures in reproducing hypoxia-dependent changes observed in the TME.
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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.