ArticleThe Journal of clinical investigation2022
Targeting HIF-1α abrogates PD-L1-mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 126 citations in OpenAlex.
- Advancing the understanding of the immune escape in lung cancer immunotherapy: Global trends, collaborations, and future directions.Human vaccines & immunotherapeutics · 2026Article
- A meta-interaction basis for cell-cell communication in tissues.bioRxiv : the preprint server for biology · 2026Article
- Review
- CRACD loss drives hypoxia-induced immune escape in gastric cancer.Nature communications · 2026Article
- A Multiple Enzyme-Mimetic Platinum-Ruthenium Nanohybrid Prodrug Potentiates Chemo-/Chemodynamic-/Immuno-Therapy of Hypoxic Tumors.Advanced healthcare materials · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma.Nature communications · 2026Article
- Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies.Molecular carcinogenesis · 2026Review
- Article
- Integrated hypoxia and metabolic gene signature to predict clinical outcomes and therapeutic vulnerabilities in lung adenocarcinoma.Journal of thoracic disease · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Preoperative low-attenuation area on computed tomography is associated with recurrence after curative resection for non-small-cell lung cancer.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Review
- Early Recurrence of HCC Is Driven by Inflammation-Related HIF-1α Independent Angiogenesis Rather than Hypoxia-Induced Immune Escape.Biomolecules · 2026Article
- Review
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy.Materials today. Bio · 2026Article
- Hypoxia and HIF signalling in tumour microenvironment: linking immune evasion, metabolic rewiring and epigenetic regulation.Expert reviews in molecular medicine · 2026Review
- When Checkpoint Inhibitors Break Barriers: Mechanisms and Challenges of irAEs of the Skin, Gastrointestinal Tract, and Lung.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
A combination of anti-CTLA-4 plus anti-PD-1/PD-L1 is the most effective cancer immunotherapy but causes high incidence of immune-related adverse events (irAEs). Here we report that targeting of HIF-1α suppressed PD-L1 expression on tumor cells and tumor-infiltrating myeloid cells, but unexpectedly induced PD-L1 in normal tissues by an IFN-γ-dependent mechanism. Targeting the HIF-1α/PD-L1 axis in tumor cells reactivated tumor-infiltrating lymphocytes and caused tumor rejection. The HIF-1α inhibitor echinomycin potentiated the cancer immunotherapeutic effects of anti-CTLA-4 therapy, with efficacy comparable to that of anti-CTLA-4 plus anti-PD-1 antibodies. However, while anti-PD-1 exacerbated irAEs triggered by ipilimumab, echinomycin protected mice against irAEs by increasing PD-L1 levels in normal tissues. Our data suggest that targeting HIF-1α fortifies the immune tolerance function of the PD-1/PD-L1 checkpoint in normal tissues but abrogates its immune evasion function in the tumor microenvironment to achieve safer and more effective immunotherapy.
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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.