ArticleAmerican journal of cancer research2022
Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles.
Article in American journal of cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- CEST-MRI assessment of locally advanced pMMR rectal cancer for prediction of immune activation status following radiotherapy.European radiology · 2026Article
- Cytotoxicity and immunogenic cell death studies of water-soluble tetrahedral Ga(iii) or Fe(iii) coordination cages containing a Au(i) anticancer drug as guest.Inorganic chemistry frontiers · 2026Article
- Beyond the chaos: How architecture structures tumour biology.The FEBS journal · 2026Review
- Chloride Intracellular Channel 2 Can Function as a Malignant Factor in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- Evaluation of Trilysine-Cross-Linked Gellan Gum for Intratumoral Delivery of Anti-PD-1 in a Colorectal Cancer Mouse Tumor Model.ACS biomaterials science & engineering · 2026Article
- 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
- Acidosis regulates immune progression in rheumatoid arthritis by promoting the expression of cytokines and co-stimulatory molecules in synovial fibroblasts.Molecular medicine (Cambridge, Mass.) · 2025Article
- Acidity and hypoxia of tumor microenvironment, a positive interplay in extracellular vesicle release by tumor cells.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Stimuli-Responsive Liposomes of 5-Fluorouracil: Progressive Steps for Safe and Effective Treatment of Colorectal Cancer.Pharmaceutics · 2024Review
- Review
- Eosinophils in Colorectal Cancer: Emerging Insights into Anti-Tumoral Mechanisms and Clinical Implications.International journal of molecular sciences · 2024Review
- Unveiling cytokine charge disparity as a potential mechanism for immune regulation.Cytokine & growth factor reviews · 2024Review
- The electroneutral NaAmerican journal of physiology. Cell physiology · 2024Article
- Hypoxic Conditioning: A Potential Perioperative Strategy to Reduce Abdominal Aortic Occlusion-Related Injury in Mouse Proximal and Distal Organs.Aging and disease · 2024Article
- Intracellular Acidification in a Rat C6 Glioma Model following Cariporide Injection Investigated by CEST-MRI.Metabolites · 2023Article
- Old and New Blood Markers in Human Colorectal Cancer.International journal of molecular sciences · 2022Review
- Monitoring extracellular ion and metabolite dynamics with recombinant nanobody-fused biosensors.iScience · 2022Article
- Tumor acidity: From hallmark of cancer to target of treatment.Frontiers in oncology · 2022Review
- The complex relationship between multiple drug resistance and the tumor pH gradient: a review.Cancer drug resistance (Alhambra, Calif.) · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.
Indexed as
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35141009PMC8822272W4211266935What OpenQuestion holds
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.