ArticleJournal for immunotherapy of cancer2024
Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Telmisartan enhances anti-PD-1 efficacy in MSS colorectal cancer via modulation of PD-L1 and STAT3 signaling.Translational cancer research · 2026Article
- AGTR1 signaling contributes to tumor immunity and therapy response in non-small cell lung cancer.Molecular therapy. Oncology · 2026Article
- The Impact of Angiotensin-Converting Enzyme Inhibitors on Immune-Related Adverse Events and Clinical Outcomes in Patients with Metastatic NSCLC.Biomedicines · 2026Article
- Losartan Enhances Radiosensitivity by Reversing Immunosuppressive Tumor Microenvironment Induced by Radiotherapy in TNBC.Cancer science · 2026Article
- Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances.International journal of molecular sciences · 2026Review
- Single-Cell Transcriptomics Reveals Immune Modulation by Telmisartan in Colorectal Cancer.Cells · 2026Article
- Angiotensin II type 1 receptor signaling promotes bladder cancer progression and its inhibition by Losartan.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Review
- Piezo1 as a mechanical checkpoint in T cell immunotherapy for solid tumors.Frontiers in pharmacology · 2026Review
- Identification ofFrontiers in pharmacology · 2026Article
- Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026Review
- Unveiling trends and clinical progress of immunotherapy for endometrial cancer: a scientometric and clinical trial landscape analysis.Frontiers in immunology · 2026Review
- Tumor-Promoting Crosstalk of MMP11⁺ Fibroblasts and SPP1⁺ Macrophages Drive Poor Prognosis in Breast Cancer: Integrated Multi-Omics Analysis.ImmunoTargets and therapy · 2026Article
- Collagen-mediated pro-tumorigenic MAPK activation drives stromal-immune reprogramming in solid cancers.Frontiers in immunology · 2026Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Targeting IGF1R Overcomes Armored and Cold Tumor Microenvironment and Boosts Immune Checkpoint Blockade in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting collagen in "armored and cold" tumors: Overcoming barriers to cancer therapy.Cancer pathogenesis and therapy · 2025Review
- A prognostic signature for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.Scientific reports · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade (ICB) has made remarkable achievements, but newly identified armored and cold tumors cannot respond to ICB therapy. The high prevalence of concomitant medications has huge impact on immunotherapeutic responses, but the clinical effects on the therapeutic outcome of armored and cold tumors are still unclear.
methodsIn this research, using large-scale transcriptomics datasets, the expression and potential biological functions of angiotensin II receptor 1 (AGTR1), the target of angiotensin receptor blocker (ARB), were investigated. Next, the roles of ARB in tumor cells and tumor microenvironment cells were defined by a series of in vitro and in vivo assays. In addition, the clinical impacts of ARB on ICB therapy were assessed by multicenter cohorts and meta-analysis.
resultsAGTR1 was overexpressed in armored and cold tumors and associated with poor response to ICB therapy. ARB, the inhibitor for AGTR1, only suppressed the aggressiveness of tumor cells with high AGTR1 expression, which accounted for a very small proportion. Further analysis revealed that AGTR1 was always highly expressed in cancer-associated fibroblasts (CAFs) and ARB inhibited type I collagen expression in CAFs by suppressing the RhoA-YAP axis. Moreover, ARB could also drastically reverse the phenotype of armored and cold to soft and hot in vivo, leading to a higher response to ICB therapy. In addition, both our in-house cohorts and meta-analysis further supported the idea that ARB can significantly enhance ICB efficacy.
conclusionOverall, we identify AGTR1 as a novel target in armored and cold tumors and demonstrate the improved therapeutic efficacy of ICB in combination with ARB. These findings could provide novel clinical insight into how to treat patients with refractory armored and cold tumors.
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