ArticleNature cancer2022
Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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88 citing papers in PubMed, 116 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Palmitate promotes liver metastases by decreasing neutrophil antitumour behaviour.Nature metabolism · 2026Article
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer.Molecular cancer · 2026Review
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy.Journal of pharmaceutical analysis · 2026Review
- Integrative proteomic characterization of human lung adenocarcinoma with KRAS G12 mutations reveals molecular pathogenesis.Journal of advanced research · 2026Article
- Tertiary lymphoid structure-related genes drive tumor microenvironment heterogeneity and prognostic disparities in left-Translational cancer research · 2026Article
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Immune and Stem Cell-Mediated Bactericidal Amplification and Bone Remodeling for Infection Clearance and Osteointegration.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer.iScience · 2026Article
- RARRES1 marks an immune-cold, chemoresistance-associated malignant epithelial subpopulation enriched in pancreatic ductal adenocarcinoma.Cancer immunology, immunotherapy : CII · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- A novel anoikis resistance-associated gene model for prognostic prediction and immune microenvironment characterization in lung squamous cell carcinoma.Discover oncology · 2026Article
- Elevated levels of SLC38A1 are correlated with an unfavorable prognosis, as well as accelerated cell proliferation and metastasis in lung adenocarcinoma.BMC cancer · 2026Article
- Epigenetic subtypes of high-grade T1 bladder cancer reveal intra-tumor heterogeneity and distinct interactions with tumor microenvironment.Theranostics · 2026Article
28 more citing papers are in PubMed but not listed here.
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26 authors at 6 institutions in 3 countries.
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Abstract
Solid tumors are generally characterized by an acidic tumor microenvironment (TME) that favors cancer progression, therapy resistance and immune evasion. By single-cell RNA-sequencing analysis in individuals with pancreatic ductal adenocarcinoma (PDAC), we reveal solute carrier family 4 member 4 (SLC4A4) as the most abundant bicarbonate transporter, predominantly expressed by epithelial ductal cells. Functionally, SLC4A4 inhibition in PDAC cancer cells mitigates the acidosis of the TME due to bicarbonate accumulation in the extracellular space and a decrease in lactate production by cancer cells as the result of reduced glycolysis. In PDAC-bearing mice, genetic or pharmacological SLC4A4 targeting improves T cell-mediated immune response and breaches macrophage-mediated immunosuppression, thus inhibiting tumor growth and metastases. In addition, Slc4a4 targeting in combination with immune checkpoint blockade is able to overcome immunotherapy resistance and prolong survival. Overall, our data propose SLC4A4 as a therapeutic target to unleash an antitumor immune response in PDAC.
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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.