Cyclin-Dependent Kinase Inhibitors Function as Potential Immune Regulators via Inducing Pyroptosis in Triple Negative Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35756622", "kind": "science-record", "revision": 4, "content_hash": "sha256:f2837ce152065d8b20a3819caf1719d207235bcb57bffd3ef940d884d8ef2a0e", "created_at": "2026-11-01T18:14:47Z", "updated_at": "2026-11-01T22:06:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cyclin-Dependent Kinase Inhibitors Function as Potential Immune Regulators via Inducing Pyroptosis in Triple Negative Breast Cancer.", "doi": "10.3389/fonc.2022.820696", "pmid": "35756622", "authors": ["Tao Xu", "Zhen Wang", "Jiahao Liu", "Ge Wang", "Dongchen Zhou", "Yaying Du", "Xingrui Li", "Yu Xia", "Qinglei Gao"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Immunotherapy is the most promising treatment in triple-negative breast cancer (TNBC), and its efficiency is largely dependent on the intra-tumoral immune cells infiltrations. Thus, novel ways to assist immunotherapy by increasing immune cell infiltrations were highly desirable.\nMethods: To find key immune-related genes and discover novel immune-evoking molecules, gene expression profiles of TNBC were downloaded from Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identified hub genes. The CMap database was used subsequently to predicate potential drugs that can modulate the overall hub gene expression network. In vitro experiments were conducted to assess the anti-tumor activity and the pyroptosis phenotypes induced by GW-8510.\nResults: Gene expression profiles of 198 TNBC patients were downloaded from GEO dataset GSE76124, and ssGSEA was used to divide them into Immune Cell Proficiency (ICP) group and Immune Cell Deficiency (ICD) group. Hub differential expressed gene modules between two groups were identified by WGCNA and then annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A cyclin-dependent kinase (CDK) 2 inhibitor, GW-8510 was then identified by the CMap database and further investigated. Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials.\nConclusion: GW-8510, as well as other CDK inhibitors, might serve as potential immune regulators and pyroptosis promotors in TNBC.", "claims": [{"id": "claim-method", "statement": "The WGCNA method was analyzed by Pearson correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35756622", "locator": "sections[14] \"Statistical Analysis\" paragraph 2", "quote": "The WGCNA method was analyzed by Pearson correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35756622", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35756622", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials.", "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:35756622"], "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. 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More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK", "SVA” and “hclust”. 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