{"doi":"10.1101/2022.10.03.510561","title":"T <sub>reg</sub> cells drive MYCN-mediated immunosuppression and tumor aggressiveness in high-risk neuroblastoma","abstract":"Abstract Solid tumors, especially those with aberrant MYCN activation, harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance 1,2 , yet the underlying mechanisms are elusive and effective strategies to tackle this challenge are lacking. Here we demonstrated the crucial role of T regulatory (T reg ) cells in MYCN-mediated immune repression and tumor aggression using high-risk neuroblastoma (NB) as a model system. Human MYCN-activated NB attracts CD4 + T reg cells, which are also found enriched in MYCN-high primary patient samples. Zebrafish MYCN -overexpressing neural crests recruit Cd4 + cells before tumor formation and induce an immunosuppressive microenvironment, thereby promoting tumor onset and progression. Strikingly, disruption of T reg cells through depletion of forkhead box protein 3a restores anti-tumor immunity and impairs NB development. Together, our studies establish T reg cells as the key driver of MYCN-mediated immunosuppression and tumor aggressiveness, providing mechanistic insights and therapeutic implications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304507,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9458,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":530351,"name":"Andrew Lam","orcid":"0000-0003-0036-7104","position":1,"is_corresponding":false},{"id":432198,"name":"Xu Zhang","orcid":"0000-0002-9784-0481","position":2,"is_corresponding":false},{"id":357172,"name":"Satyaki Sengupta","orcid":null,"position":3,"is_corresponding":false},{"id":89706,"name":"J. Bryan Iorgulescu","orcid":"0000-0003-1405-3667","position":4,"is_corresponding":false},{"id":997373,"name":"Tao Zuo","orcid":"0000-0002-2125-7548","position":5,"is_corresponding":false},{"id":997374,"name":"Alexander Floru","orcid":"0000-0002-9578-0411","position":6,"is_corresponding":false},{"id":674054,"name":"Grace K. Meara","orcid":"0009-0008-9201-2688","position":7,"is_corresponding":false},{"id":348965,"name":"Liang Lin","orcid":"0000-0002-3965-4103","position":8,"is_corresponding":false},{"id":997375,"name":"Kenneth O. Lloyd","orcid":"0000-0003-2343-2255","position":9,"is_corresponding":false},{"id":997376,"name":"Lauren Kwok","orcid":"0009-0001-3799-0154","position":10,"is_corresponding":false},{"id":997927,"name":"Kaylee E. Smith","orcid":null,"position":11,"is_corresponding":false},{"id":997377,"name":"Raghavendar T. Nagaraju","orcid":"0000-0002-6891-5181","position":12,"is_corresponding":false},{"id":997378,"name":"Rob Meijers","orcid":"0000-0003-2872-6279","position":13,"is_corresponding":false},{"id":621835,"name":"Craig J. Ceol","orcid":"0000-0002-7188-7580","position":14,"is_corresponding":false},{"id":22056,"name":"Ching‐Ti Liu","orcid":"0000-0002-0703-0742","position":15,"is_corresponding":false},{"id":25330,"name":"Sanda Alexandrescu","orcid":"0000-0001-9246-4184","position":16,"is_corresponding":false},{"id":3263,"name":"Catherine J. Wu","orcid":"0000-0002-3348-5054","position":17,"is_corresponding":false},{"id":25296,"name":"Derin B. Keskin","orcid":"0000-0002-8496-6181","position":18,"is_corresponding":false},{"id":267026,"name":"Rani E. George","orcid":"0000-0003-4206-1779","position":19,"is_corresponding":false},{"id":262729,"name":"Hui Feng","orcid":"0000-0003-1318-821X","position":20,"is_corresponding":false},{"id":443907,"name":"Xiaodan Qin","orcid":"0000-0002-1573-7852","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"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":[]}