ArticleCancer research2016
Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04321161 (Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm), which is not on this map. Cited by 364 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Analysis of T Cell Metabolism and Immune Phenotype in Relapsed Acute Myeloid Leukemia Patients Receiving Donor Lymphocyte Infusions and Bicanorm (Sodium Bicarbonate)
Who cites it
364 citing papers in PubMed, 572 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Site-specific metabolic and hypoxia-associated profiles in metastatic melanoma.Journal for immunotherapy of cancer · 2026Article
- Beyond gastric acid: pharmacologic modulation of the tumor microenvironment by vonoprazan and its drug-interaction implications for chemotherapy and immunotherapy.Cancer chemotherapy and pharmacology · 2026Review
- An engineered bacteria-chitosan hybrid robot for lactate depletion and synergistic STING activation to potentiate bladder cancer immunotherapy.Materials today. Bio · 2026Article
- Multimodal Imaging of Hypoxia, Metabolism and pH in Feline Sarcoma Using HyperpolarizedAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- High-Resolution Imaging of Extracellular pH in Mouse Liver Tumor.NMR in biomedicine · 2026Article
- CEST-MRI assessment of locally advanced pMMR rectal cancer for prediction of immune activation status following radiotherapy.European radiology · 2026Article
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- Longitudinal Monitoring of Metabolic Gradients in Microreactor Culture Platforms by Raman Spectroscopy.Biosensors · 2026Article
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Review
- Integrative analysis reveals the role of SUMOylation-related patterns in shaping the tumor microenvironment and predicting treatment sensitivity of colorectal cancer.Translational cancer research · 2026Article
- Lactate-mediated NK cell dysfunction as a prognostic marker and therapeutic target in breast cancer.Cell death discovery · 2026Article
- Targeting tumor-infiltrating regulatory T cells based on immunometabolism.Cancer biology & medicine · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Beyond Epilepsy Control: Repurposing Antiepileptic Drugs in Central Nervous System Tumor Therapy.Cells · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
304 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation.
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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.