{"doi":"10.1172/jci181471","title":"IL-7–mediated expansion of autologous lymphocytes increases CD8+ VLA-4 expression and accumulation in glioblastoma models","abstract":"The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused nonantigen specific autologous lymphocytes could accumulate in intracranial tumors. We observed that nonspecific autologous CD8+ ALT cells can indeed accumulate in this context, despite endogenous T cell sequestration in bone marrow. Rates of intratumoral accumulation were markedly increased when expanding lymphocytes with IL-7 compared with IL-2. Pretreatment with IL-7 ALT also enhanced the efficacy of multiple tumor-specific and nontumor-specific T cell-dependent immunotherapies against orthotopic murine and human xenograft gliomas. Mechanistically, we detected increased VLA-4 on mouse and human CD8+ T cells following IL-7 expansion, with increased transcription of genes associated with migratory integrin expression (CD9). We also observed that IL-7 increases S1PR1 transcription in human CD8+ T cells, which we have shown to be protective against tumor-induced T cell sequestration. These observations demonstrate that expansion with IL-7 enhances the capacity of ALT to accumulate within intracranial tumors and that pretreatment with IL-7 ALT can boost the efficacy of subsequent T cell-activating therapies against glioma. Our findings will inform the development of future clinical trials where ALT pretreatment can be combined with T cell-activating therapies.","journal":"Journal of Clinical Investigation","year":2025,"id":520977,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.937,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255889,"name":"Kelly Hotchkiss","orcid":"0000-0001-9175-1579","position":1,"is_corresponding":false},{"id":499625,"name":"Sarah Cook","orcid":"0000-0002-0516-9388","position":2,"is_corresponding":false},{"id":1391277,"name":"Pamy Noldner","orcid":null,"position":3,"is_corresponding":false},{"id":383894,"name":"Ying Zhou","orcid":"0000-0003-3607-8216","position":4,"is_corresponding":false},{"id":1391278,"name":"Eliese Moelker","orcid":null,"position":5,"is_corresponding":false},{"id":1391279,"name":"Chelsea Railton","orcid":null,"position":6,"is_corresponding":false},{"id":1390863,"name":"Emily Blandford","orcid":"0009-0000-7440-3185","position":7,"is_corresponding":false},{"id":556031,"name":"Bhairavy Puviindran","orcid":"0000-0002-8827-0050","position":8,"is_corresponding":false},{"id":1391280,"name":"Shannon E. Wallace","orcid":null,"position":9,"is_corresponding":false},{"id":733404,"name":"Pamela K. Norberg","orcid":null,"position":10,"is_corresponding":false},{"id":272861,"name":"Gary E. Archer","orcid":null,"position":11,"is_corresponding":false},{"id":271754,"name":"Beth H. Shaz","orcid":"0000-0002-2270-4821","position":12,"is_corresponding":false},{"id":256583,"name":"Katayoun Ayasoufi","orcid":"0000-0002-3797-0823","position":13,"is_corresponding":false},{"id":268105,"name":"John H. Sampson","orcid":"0000-0002-0104-7658","position":14,"is_corresponding":false},{"id":268104,"name":"Mustafa Khasraw","orcid":"0000-0003-3249-9849","position":15,"is_corresponding":false},{"id":564965,"name":"Peter E. Fecci","orcid":"0000-0002-2912-8695","position":16,"is_corresponding":false},{"id":669774,"name":"Kirit Singh","orcid":"0000-0002-0419-5381","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40244705","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":[]}