ArticleThe Journal of clinical investigation2021
Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026Review
- Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours.Nature communications · 2026Article
- ATF7ip Inhibits the Tumor Immune Response by Promoting Terminal CD8+ T-cell Exhaustion.Cancer immunology research · 2026Article
- Targeting mitochondrial α-ketoglutarate sequestration disables dual oncogenic drivers and metabolic adaptability in pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- Comprehensive longitudinal profiling identifies differential frequency, epitope specificity, and effector function of CD8EBioMedicine · 2026Article
- Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function.Cell · 2026Article
- Article
- HIF-1αImmunity · 2026Article
- Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory.Nature immunology · 2026Article
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- Higher proximity of PD-L1Translational lung cancer research · 2026Article
- Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function.bioRxiv : the preprint server for biology · 2026Article
- Lactate transmission from hypoxic tumor cells promotes macrophage senescence and M2 polarization via the DNMT1-NHE7 axis to accelerate endometrial cancer progression.Cell death & disease · 2026Article
- Hypoxia-Associated Molecular Subtypes Reveal Immune Checkpoint, Ferroptosis, and m6A Regulatory Heterogeneity in Pediatric Vasculitis.Human mutation · 2026Article
- Tumor-embedded Immunity and TRM Cell Functions in Cancer.Mini reviews in medicinal chemistry · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Clinical-scale 10-day TCR-T cell manufacturing using IL-2/7/15 and TGF-β promotes early memory and tissue-resident-like phenotypes and robust antitumor activityFrontiers in immunology · 2026Article
- Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2025Article
- Tissue-Resident Memory T Cells in Rheumatoid Immune Diseases: Pathogenic Mechanisms and Therapeutic Strategies.Biomedicines · 2025Review
36 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
14 authors at 3 institutions in 1 country.
Funding
Abstract
Adoptive T cell therapies (ACTs) hold great promise in cancer treatment, but low overall response rates in patients with solid tumors underscore remaining challenges in realizing the potential of this cellular immunotherapy approach. Promoting CD8+ T cell adaptation to tissue residency represents an underutilized but promising strategy to improve tumor-infiltrating lymphocyte (TIL) function. Here, we report that deletion of the HIF negative regulator von Hippel-Lindau (VHL) in CD8+ T cells induced HIF-1α/HIF-2α-dependent differentiation of tissue-resident memory-like (Trm-like) TILs in mouse models of malignancy. VHL-deficient TILs accumulated in tumors and exhibited a core Trm signature despite an exhaustion-associated phenotype, which led to retained polyfunctionality and response to αPD-1 immunotherapy, resulting in tumor eradication and protective tissue-resident memory. VHL deficiency similarly facilitated enhanced accumulation of chimeric antigen receptor (CAR) T cells with a Trm-like phenotype in tumors. Thus, HIF activity in CD8+ TILs promotes accumulation and antitumor activity, providing a new strategy to enhance the efficacy of ACTs.
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What OpenQuestion holds
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.