ArticleJournal for immunotherapy of cancer2018
Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy.
Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- SPRED2 Negatively Regulates CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunological Drug-Drug Interactions in Immune Checkpoint Inhibitor Therapy: Mechanisms, Clinical Evidence, and Artificial Intelligence.Current oncology reports · 2026Review
- CD8 immunoPET imaging to stratify response and guide combination immunotherapy and radiation in triple negative breast cancer.Breast cancer research : BCR · 2026Article
- Single-Cell Transcriptomics Reveals Immune Modulation by Telmisartan in Colorectal Cancer.Cells · 2026Article
- Unraveling tumor cell‑tumor microenvironment crosstalk through antibody array technologies (Review).International journal of oncology · 2025Review
- Radiomics-Based Unsupervised Clustering Identifies Subtypes Associated With Prognosis and Immune Microenvironment in Clear Cell Renal Cell Carcinoma: A Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endothelial Per-Arnt-Sim domain-containing protein 1 expression is correlated with poor prognosis and promotes invasion and metastasis in gastric cancer.World journal of gastrointestinal oncology · 2025Article
- The effect of concomitant drugs on oncological outcomes in patients treated with immunotherapy for metastatic urothelial carcinoma: a narrative review.Oncology research · 2025Review
- Application of Carbon Nanomaterials to Enhancing Tumor Immunotherapy: Current Advances and Prospects.International journal of nanomedicine · 2024Review
- Unlocking the tumor-immune microenvironment in osteosarcoma: insights into the immune landscape and mechanisms.Frontiers in immunology · 2024Review
- High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight.Molecular biology reports · 2023Review
- The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.Cancer cell international · 2023Review
- Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy.Pharmaceutics · 2023Review
- Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy.The oncologist · 2023Article
- Engineering an active immunotherapy for personalized cancer treatment and prevention of recurrence.Science advances · 2023Article
- Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications.Cancers · 2023Review
- System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy.Pharmaceutics · 2023Article
- The use of angiotensin system inhibitors correlates with longer survival in resected pancreatic adenocarcinoma patients.HPB : the official journal of the International Hepato Pancreato Biliary Association · 2023Article
- Host-Derived Cytotoxic Agents in Chronic Inflammation and Disease Progression.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism.
resultsHere, using 4T1 and CT26 syngeneic mouse tumor models, we found that local AngII in the tumor microenvironment was involved in immune escape of tumour cells and an AngII signaling blockage sensitized tumours to checkpoint immunotherapy. Furthermore, an AngII signaling blockage reversed the tumor immunosuppressive microenvironment, and inhibition of angiotensinogen (AGT, a precursor of AngII) expression strongly triggered an immune-activating cytokine profile in hypoxic mouse cancer cells. More importantly, AGT silencing combined with a checkpoint blockage generated an abscopal effect in resistant tumors.
conclusionOur study demonstrated an important role of local AngII in the formation of a tumor immunosuppressive microenvironment and its blockage may enhance tumor sensitivity to checkpoint immunotherapy. The combination of an AngII signaling blocker and an immune-checkpoint blockage could be a promising strategy to improve tumors responses to current checkpoint 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.