CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35155218", "kind": "science-record", "revision": 6, "content_hash": "sha256:7910d9a12be31af582a00428e3dc0213fc165269f01f48e342234a55ce5d3c06", "created_at": "2026-11-01T17:36:54Z", "updated_at": "2026-11-01T22:48:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CA9-Related Acidic Microenvironment Mediates CD8+ T Cell Related Immunosuppression in Pancreatic Cancer.", "doi": "10.3389/fonc.2021.832315", "pmid": "35155218", "authors": ["Lingdi Yin", "Yichao Lu", "Cheng Cao", "Zipeng Lu", "Jishu Wei", "Xiaole Zhu", "Jianmin Chen", "Feng Guo", "Min Tu", "Chunhua Xi", "Kai Zhang", "Junli Wu", "Wentao Gao", "Kuirong Jiang", "Yi Miao", "Qiang Li", "Yunpeng Peng"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "PURPOSE: This study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays.\nMETHODS: Expression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD_CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells.\nRESULTS: The CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD_CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration.\nCONCLUSION: Pancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy.", "claims": [{"id": "claim-method", "statement": "Gene differential expression analysis were performed using R/Bioconductor edgeR.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35155218", "locator": "sections[4] \"Bioinformatical Methodology\" paragraph 2", "quote": "Gene differential expression analysis were performed using R/Bioconductor edgeR."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35155218", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Low CD8+ T cell infiltration is significantly correlated with poor prognosis of pancreatic cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35155218", "locator": "sections[13] \"CD8+ T Cells Predicts Poor Prognosis in PDAC\" paragraph 2", "quote": "According to the bioinformatics analysis of TCGA transcriptome data, among the 22 immune microenvironment components, low CD8+ T cell infiltration is significantly correlated with poor prognosis of pancreatic cancer ( Figure 1B )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Low CD8+ T cell infiltration is significantly correlated with poor prognosis of pancreatic cancer.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35155218"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE131050"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE131050"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35155218", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.832315", "sha256": "sha256:5f1ef276a9fd1dcfbf360e1130e279866142019cd2ef5fd47f7d385f26dcc474", "bytes": 34880, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2021.832315", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8828571", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE131050", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE131050", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE131050", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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METHODS: Expression data and clinico", "CA9 expression and up-regulate CD8+ T cells in vivo. (B) TMA IHC analysis showed that CA9 high e"], "order_basis": "paper_text_order:348", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["using standard techniques. Pancreatic cancer cell lines were cultured in DMEM supplemented with 10% FBS, penicilli", "echniques. Pancreatic cancer cell lines were cultured in DMEM supplemented with 10% FBS, penicillin (", "ancer cell lines and the isolated PBMCs were cultured in DMEM, supplemented with 10% FBS, 100U/ml pen"], "order_basis": "paper_text_order:3687", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["nd up-regulate CD8+ T cells in vivo. 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