RGD Reference Report - pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma.

Authors: Kuchuk, Olga  Tuccitto, Alessandra  Citterio, Davide  Huber, Veronica  Camisaschi, Chiara  Milione, Massimo  Vergani, Barbara  Villa, Antonello  Alison, Malcolm Ronald  Carradori, Simone  Supuran, Claudiu T  Rivoltini, Licia  Castelli, Chiara  Mazzaferro, Vincenzo 
Citation: Kuchuk O, etal., Oncoimmunology. 2018 Mar 26;7(7):e1445452. doi: 10.1080/2162402X.2018.1445452. eCollection 2018.
RGD ID: 155226869
Pubmed: PMID:29900055   (View Abstract at PubMed)
PMCID: PMC5993489   (View Article at PubMed Central)
DOI: DOI:10.1080/2162402X.2018.1445452   (Journal Full-text)

Interfering with tumor metabolism is an emerging strategy for treating cancers that are resistant to standard therapies. Featuring a rapid proliferation rate and exacerbated glycolysis, hepatocellular carcinoma (HCC) creates a highly hypoxic microenvironment with excessive production of lactic and carbonic acids. These metabolic conditions promote disease aggressiveness and cancer-related immunosuppression. The pH regulatory molecules work as a bridge between tumor cells and their surrounding milieu. Herein, we show that the pH regulatory molecules CAIX, CAXII and V-ATPase are overexpressed in the HCC microenvironment and that interfering with their pathways exerts antitumor activity. Importantly, the V-ATPase complex was expressed by M2-like tumor-associated macrophages. Blocking ex vivo V-ATPase activity established a less immune-suppressive tumor microenvironment and reversed the mesenchymal features of HCC. Thus, targeting the unique cross-talk between tumor cells and the tumor microenvironment played by pH regulatory molecules holds promise as a strategy to control HCC progression and to reduce the immunosuppressive pressure mediated by the hypoxic/acidic metabolism, particularly considering the potential combination of this strategy with emerging immune checkpoint-based immunotherapies.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CA12Humanhepatocellular carcinoma  IEP mRNA:altered expression:liverRGD 
CA9Humanhepatocellular carcinoma  IEP mRNA:altered expression:liverRGD 
Car12Rathepatocellular carcinoma  ISOCA12 (Homo sapiens)mRNA:altered expression:liverRGD 
Car12Mousehepatocellular carcinoma  ISOCA12 (Homo sapiens)mRNA:altered expression:liverRGD 
Car9Rathepatocellular carcinoma  ISOCA9 (Homo sapiens)mRNA:altered expression:liverRGD 
Car9Mousehepatocellular carcinoma  ISOCA9 (Homo sapiens)mRNA:altered expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Car12  (carbonic anhydrase 12)
Car9  (carbonic anhydrase 9)

Genes (Mus musculus)
Car12  (carbonic anhydrase 12)
Car9  (carbonic anhydrase 9)

Genes (Homo sapiens)
CA12  (carbonic anhydrase 12)
CA9  (carbonic anhydrase 9)


Additional Information