ArticleBMC cancer2022
The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.Cellular & molecular biology letters · 2026Pooled it
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Flavonoid-modulated JAK-STAT signaling mitigates malignant transformation and drug resistance in breast tumors: A clinically relevant 3PM-guided innovation.Journal of advanced research · 2026Review
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- Low pH, High Stakes: A Narrative Review Exploring the Acid-Sensing GPR65 Pathway as a Novel Approach in Renal Cell Carcinoma.Cancers · 2025Review
- The Roles of STAT3 and STAT5 in Breast Cancer.Cancers · 2025Review
- Potentiation of immune checkpoint blockade with a pH-sensitizer as monitored in two pre-clinical tumor models with acidoCEST MRI.British journal of cancer · 2025Article
- Harnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective.The FEBS journal · 2025Review
- Advancing Breast Cancer Treatment: The Role of Immunotherapy and Cancer Vaccines in Overcoming Therapeutic Challenges.Vaccines · 2025Review
- Exploring Natural Compounds Targeting PD-L1 and STAT3: Toxicogenomic Analysis, Virtual Screening, Molecular Docking, ADMET Evaluation, and Biological Activity Prediction.Current computer-aided drug design · 2025Article
- Article
- Hallmarks of cancer resistance.iScience · 2024Review
- A NIR-Fluorochrome for Live Cell Dual Emission and Lifetime Tracking from the First Plasma Membrane Interaction to Subcellular and Extracellular Locales.Molecules (Basel, Switzerland) · 2024Article
- Impact of Acute or Chronic Acidosis and Hypoxia on Gene Expression Patterns in Tumour Cells: Potential Functional Implications.Advances in experimental medicine and biology · 2024Article
- Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors.Molecular cancer · 2023Article
- How protons pave the way to aggressive cancers.Nature reviews. Cancer · 2023Review
- Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model.Cancers · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.
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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.