ArticleThe Journal of experimental medicine2022
IL-17-induced HIF1α drives resistance to anti-PD-L1 via fibroblast-mediated immune exclusion.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 47 citations in OpenAlex.
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- Review
- Contextualizing TNature reviews. Immunology · 2026Review
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- The Double-Edged Sword of Type 17 Immunity in Wound Healing and Skin Barrier Repair: Microenvironment-Driven Functional Plasticity.Biomolecules · 2026Review
- Expression Analysis ofIranian journal of medical sciences · 2026Article
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Multi-omics analysis unveils the role of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.Cancer cell international · 2025Article
- Computer-Aided Drug Design Across Breast Cancer Subtypes: Methods, Applications and Translational Outlook.International journal of molecular sciences · 2025Review
- IL-17A blockade alleviates immune checkpoint inhibitor-associated psoriasiform rash: preclinical and clinical responses.Cancer biology & medicine · 2025Article
- New strategies to enhance the efficacy of PD-1/PD-L1 inhibitors in treating microsatellite stable colorectal cancer.Future oncology (London, England) · 2025Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.Molecular cancer · 2025Article
- Molecular and cellular dynamics of squamous cell carcinomas across tissues.Genes & development · 2025Review
- Overexpression of ORAOV1 and its association with immunotherapy resistance in hepatocellular carcinoma.PeerJ · 2025Article
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Revisiting the role of cancer-associated fibroblasts in tumor microenvironment.Frontiers in immunology · 2025Review
- Role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer (Review).Oncology reports · 2024Review
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13 authors at 3 institutions in 1 country.
Funding
Abstract
Increasing evidence suggests that intratumoral inflammation has an outsized influence on antitumor immunity. Here, we report that IL-17, a proinflammatory cytokine widely associated with poor prognosis in solid tumors, drives the therapeutic failure of anti-PD-L1. By timing the deletion of IL-17 signaling specifically in cancer-associated fibroblasts (CAFs) in late-stage tumors, we show that IL-17 signaling drives immune exclusion by activating a collagen deposition program in murine models of cutaneous squamous cell carcinoma (cSCC). Ablation of IL-17 signaling in CAFs increased the infiltration of cytotoxic T cells into the tumor mass and sensitized otherwise resistant cSCC to anti-PD-L1 treatment. Mechanistically, the collagen deposition program in CAFs was driven by IL-17-induced translation of HIF1α, which was mediated by direct binding of Act1, the adaptor protein of IL-17 receptor, to a stem-loop structure in the 3' untranslated region (UTR) in Hif1α mRNA. Disruption of Act1's binding to Hif1α mRNA abolished IL-17-induced collagen deposition and enhanced anti-PD-L1-mediated tumor regression.
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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.