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We investigated whether peripherally infused non-antigen specific autologous lymphocytes (ALT) could accumulate in intracranial tumors. We observed that non-specific autologous CD8\n                  <jats:sup>+<\/jats:sup>\n                  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 to IL-2. Pre-treatment with IL-7 ALT also enhanced the efficacy of multiple tumor-specific and non-tumor-specific T cell-dependent immunotherapies against orthotopic murine and human xenograft gliomas. Mechanistically, we detected increased VLA-4 on mouse and human CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells following IL-7 expansion, with increased transcription of genes associated with migratory integrin expression (\n                  <jats:italic>CD9)<\/jats:italic>\n                  . We also observed that IL-7 increases\n                  <jats:italic>S1PR1<\/jats:italic>\n                  transcription in human CD8\n                  <jats:sup>+<\/jats:sup>\n                  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 pre-treatment 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 pre-treatment can be combined with T cell-activating therapies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Brief Summary<\/jats:title>\n                  <jats:p>T cell immunotherapies are limited by few T cells in glioma. Adoptively transferred lymphocytes expanded with IL-7 exhibit increased VLA-4 expression and accumulate in tumors.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.04.01.587634","type":"posted-content","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T23:55:22Z","timestamp":1712015722000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-7-mediated expansion of autologous lymphocytes increases CD8\n                  <sup>+<\/sup>\n                  VLA-4 expression and accumulation in glioblastoma models"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0419-5381","authenticated-orcid":false,"given":"Kirit","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Hotchkiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamy","family":"Noldner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliese M.","family":"Moelker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea O.","family":"Railton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E.","family":"Blandford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhairavy J.","family":"Puviindran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela K.","family":"Norberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth H.","family":"Shaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3797-0823","authenticated-orcid":false,"given":"Katayoun","family":"Ayasoufi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Khasraw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Fecci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025052500184934000_2024.04.01.587634v4.1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd1524"},{"key":"2025052500184934000_2024.04.01.587634v4.2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-19-1068"},{"key":"2025052500184934000_2024.04.01.587634v4.3","doi-asserted-by":"publisher","DOI":"10.1097\/cco.0000000000000869"},{"key":"2025052500184934000_2024.04.01.587634v4.4","doi-asserted-by":"crossref","unstructured":"Tomaszewski WH , Waibl-Polania J , Miggelbrink AM , Chakraborty MA , Fecci PE , Sampson JH , et al. 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