ArticleMolecular cancer2023
Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors.
Article in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07450833 (Assessing the Safety, Tolerability and Pharmacokinetics of Benfo-Oxythiamine), which is not on this map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Assessing the Safety, Tolerability and Pharmacokinetics of Benfo-Oxythiamine (B-OT) in Healthy Volunteers - An Open Label, Phase I Study
Who cites it
61 citing papers in PubMed, 66 citations in OpenAlex.
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- Recent progress in small molecules targeting the acidic tumor microenvironment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects.Signal transduction and targeted therapy · 2026Review
- Combined Anti-PD-1/PD-L1 and Anti-angiogenic Therapy: An Emerging Direction for Future NSCLC Treatment.Current treatment options in oncology · 2026Review
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.Signal transduction and targeted therapy · 2026Article
- Acidosis-associated gene signature defines novel subtypes and dual-target therapeutic candidates in breast cancer.Journal of translational medicine · 2026Article
- Sphingosine-1-Phosphate Promotes FOS Activation in Osteosarcoma Under Tumor Acidosis.Acta physiologica (Oxford, England) · 2026Article
- T cell fate regulation in EBV‑associated nasopharyngeal carcinoma (Review).Oncology reports · 2026Review
- Review
- Noninvasive in vivo imaging of NF-κB activation predicts immunotherapy response in solid tumors.Npj imaging · 2026Article
- NIPAL1 Drives a Metabolic-Epigenetic Feedback Loop to Promote Lactate-Mediated Immune Evasion in Esophageal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Expansion of IL-2-independent tumor-infiltrating lymphocytes through a feeder-free process: a preclinical study for solid tumors.Cancer biology & medicine · 2026Article
- ICIsc: A Deep Learning Framework for Predicting Immune Checkpoint Inhibitor Response by Integrating scRNA-Seq and Protein Language Models.Bioengineering (Basel, Switzerland) · 2026Article
- Non-invasive visualization of pH changes within the tumor-micro-environment by positron emission tomography.EJNMMI research · 2026Article
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by the heterogeneous and hypoxic tumor microenvironment (TME) of solid tumors. In the TME, programmed death-ligand 1 (PD-L1) expression on cancer cells is mainly regulated by Interferon-gamma (IFN-γ), which induces T cell exhaustion and enables tumor immune evasion. In this study, we demonstrate that acidosis, a common characteristic of solid tumors, significantly increases IFN-γ-induced PD-L1 expression on aggressive cancer cells, thus promoting immune escape. Using preclinical models, we found that acidosis enhances the genomic expression and phosphorylation of signal transducer and activator of transcription 1 (STAT1), and the translation of STAT1 mRNA by eukaryotic initiation factor 4F (elF4F), resulting in an increased PD-L1 expression. We observed this effect in murine and human anti-PD-L1-responsive tumor cell lines, but not in anti-PD-L1-nonresponsive tumor cell lines. In vivo studies fully validated our in vitro findings and revealed that neutralizing the acidic extracellular tumor pH by sodium bicarbonate treatment suppresses IFN-γ-induced PD-L1 expression and promotes immune cell infiltration in responsive tumors and thus reduces tumor growth. However, this effect was not observed in anti-PD-L1-nonresponsive tumors. In vivo experiments in tumor-bearing IFN-γ
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