{"doi":"10.1101/2022.08.12.502093","title":"A microglia-CD4 <sup>+</sup> T cell partnership generates protective anti-tumor immunity to glioblastoma","abstract":"Summary The limited efficacy of immunotherapies against glioblastoma illustrates the urgent need to better understand the interactions between the central nervous system and the immune system. Here, we showed that a protective response to αCTLA-4 therapy depended on a mutualistic relationship between microglia and CD4 + T cells. Suppression of gliomas by CD4 + T cells did not require tumor-intrinsic MHC-II expression, but rather was dependent on the selective expression of MHC-II and antigen presentation by local microglia that in turn, sustained CD4 + T cell tumoricidal effector functions. CD4 + T cell secretion of IFNγ made the glioma cells vulnerable to enhanced tumor surveillance and phagocytosis by microglia via the AXL/MER tyrosine kinase receptors that were necessary for tumor suppression. This work illustrates a novel partnership between CD4 + T cells and microglia that unleashes the tumoricidal properties of microglia that can be harnessed to improve immunotherapies for glioblastoma.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304040,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"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":615026,"name":"Siva Karthik Varanasi","orcid":"0000-0001-5797-2984","position":1,"is_corresponding":false},{"id":2730,"name":"Toshiro Hara","orcid":"0000-0002-4389-3393","position":2,"is_corresponding":false},{"id":996454,"name":"Kacie A. Traina","orcid":"0000-0002-7799-3253","position":3,"is_corresponding":false},{"id":569835,"name":"Bryan McDonald","orcid":"0000-0003-1744-3433","position":4,"is_corresponding":false},{"id":267838,"name":"Yagmur Farsakoglu","orcid":"0000-0003-2503-906X","position":5,"is_corresponding":false},{"id":996872,"name":"Josh Clanton","orcid":null,"position":6,"is_corresponding":false},{"id":712668,"name":"Shihao Xu","orcid":"0000-0001-5528-8353","position":7,"is_corresponding":false},{"id":84654,"name":"Thomas H. Mann","orcid":"0000-0002-3821-1466","position":8,"is_corresponding":false},{"id":996455,"name":"Victor Y. Du","orcid":"0000-0002-2759-0114","position":9,"is_corresponding":false},{"id":84628,"name":"H. Kay Chung","orcid":"0000-0002-7028-2432","position":10,"is_corresponding":false},{"id":615025,"name":"Ziyan Xu","orcid":"0000-0003-1270-135X","position":11,"is_corresponding":false},{"id":84646,"name":"Victoria Tripple","orcid":null,"position":12,"is_corresponding":false},{"id":996456,"name":"Eduardo Casillas","orcid":"0000-0001-9968-565X","position":13,"is_corresponding":false},{"id":996457,"name":"Shixin Ma","orcid":"0000-0002-7724-3807","position":14,"is_corresponding":false},{"id":58970,"name":"Carolyn O’Connor","orcid":"0000-0002-3301-7912","position":15,"is_corresponding":false},{"id":84650,"name":"Qiyuan Yang","orcid":"0000-0001-6204-9094","position":16,"is_corresponding":false},{"id":267199,"name":"Ye Zheng","orcid":"0000-0001-5012-4309","position":17,"is_corresponding":false},{"id":25159,"name":"Tony Hunter","orcid":"0000-0002-7691-6993","position":18,"is_corresponding":false},{"id":232737,"name":"Greg Lemke","orcid":"0000-0001-5805-9855","position":19,"is_corresponding":false},{"id":267842,"name":"Susan M. Kaech","orcid":"0000-0002-3339-8698","position":20,"is_corresponding":false},{"id":996453,"name":"Dan Chen","orcid":"0000-0001-5156-6635","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T00:32:28.468841Z","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":[]}