{"doi":"10.3390/cancers16203459","title":"CCL21 Induces Plasmacytoid Dendritic Cell Migration and Activation in a Mouse Model of Glioblastoma","abstract":"Dendritic cells (DCs) are professional antigen-presenting cells that are traditionally divided into two distinct subsets: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). pDCs are known for their ability to secrete large amounts of cytokine type I interferons (IFN- α). In our previous work, we have demonstrated that pDC infiltration promotes glioblastoma (GBM) tumor immunosuppression through decreased IFN-α secretion via TLR-9 signaling and increased suppressive function of regulatory T cells (Tregs) via increased IL-10 secretion, resulting in poor overall outcomes in mouse models of GBM. Further dissecting the overall mechanism of pDC-mediated GBM immunosuppression, in this study, we identified CCL21 as highly upregulated by multiple GBM cell lines, which recruit pDCs to tumor sites via CCL21-CCR7 signaling. Furthermore, pDCs are activated by CCL21 in the GBM microenvironment through intracellular signaling of β-arrestin and CIITA. Finally, we found that CCL21-treated pDCs directly suppress CD8+ T cell proliferation without affecting regulatory T cells (Tregs) differentiation, which is considered the canonical pathway of immunotolerant regulation. Taken together, our results show that pDCs play a multifaced role in GBM immunosuppression, and CCL21 could be a novel therapeutic target in GBM to overcome pDC-mediated immunosuppression.","journal":"Cancers","year":2024,"id":429600,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"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":702406,"name":"Jack Shireman","orcid":"0000-0002-5088-7805","position":1,"is_corresponding":false},{"id":1232276,"name":"Samantha M Probelsky","orcid":"0000-0002-8316-6203","position":2,"is_corresponding":false},{"id":1232742,"name":"Bailey Rigg","orcid":null,"position":3,"is_corresponding":false},{"id":911146,"name":"Xiaohu Wang","orcid":"0009-0005-0876-3680","position":4,"is_corresponding":false},{"id":1232743,"name":"Wei Huff","orcid":null,"position":5,"is_corresponding":false},{"id":1232277,"name":"Jae Hyun Kwon","orcid":"0000-0001-7303-770X","position":6,"is_corresponding":false},{"id":471182,"name":"Mahua Dey","orcid":"0000-0002-7024-5164","position":7,"is_corresponding":false},{"id":1232275,"name":"Lei Zhao","orcid":"0000-0003-1178-1183","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:59:11.328802Z","pmid":"39456552","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":[]}