{"doi":"10.1007/s11060-024-04766-4","title":"The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues","abstract":"PURPOSE: Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high-grade glioma and human glioblastomas share many molecular similarities, including the accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford to target the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic glioma model. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma. METHODS: We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine. RESULTS: T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines, and expression increased when exposed to Tregs but not CD4 + helper T-cells. CONCLUSION: Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.","journal":"Journal of Neuro-Oncology","year":2024,"id":438770,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":730923,"name":"Ryan G. Toedebusch","orcid":null,"position":1,"is_corresponding":false},{"id":972813,"name":"Bridget McLaughlin","orcid":"0000-0001-5801-3996","position":2,"is_corresponding":false},{"id":279126,"name":"Peter J. Dickinson","orcid":"0000-0002-0037-2619","position":3,"is_corresponding":false},{"id":1249406,"name":"J. E. Van Dyke","orcid":null,"position":4,"is_corresponding":false},{"id":279130,"name":"Kevin Woolard","orcid":"0000-0003-3588-9359","position":5,"is_corresponding":false},{"id":341476,"name":"Michael E. Berens","orcid":"0000-0002-3382-6787","position":6,"is_corresponding":false},{"id":291806,"name":"Maciej S. Lesniak","orcid":"0000-0002-0096-5107","position":7,"is_corresponding":false},{"id":1249407,"name":"B.K. Sturges","orcid":null,"position":8,"is_corresponding":false},{"id":749288,"name":"Karen M. Vernau","orcid":"0000-0002-8062-0028","position":9,"is_corresponding":false},{"id":115710,"name":"C. Li","orcid":null,"position":10,"is_corresponding":false},{"id":294787,"name":"Jason Miska","orcid":"0000-0001-9608-2810","position":11,"is_corresponding":false},{"id":730400,"name":"Christine M. Toedebusch","orcid":"0000-0002-3216-3344","position":12,"is_corresponding":false},{"id":401407,"name":"Wojciech K. Panek","orcid":"0000-0002-5667-5715","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:00:43.618468Z","pmid":"39046599","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}