biostudies-literatureSingh KNINDS NIH HHSNCI NIH HHSNational Institutes of HealthAdaptin Bioe181471https://www.ebi.ac.uk/biostudies/studies/S-EPMC12165802biostudies-literatureUnknown135(12)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 andThe Journal of clinical investigationIL-7-mediated expansion of autologous lymphocytes increases CD8+ VLA-4 expression and accumulation in glioblastoma models.PMC12165802R01 CA175517P50 CA190991U01 NS090284393001670R01 CA235612P01 CA225622R01 NS099463P50-CA190991,P01-CA225622,U01-NS090284,R01-NS099463,R01-CA175517,R01-CA235612Cook SLBlandford EEZhou YNoldner PMoelker EMPuviindran BJArcher GEFecci PEWallace SEKhasraw MSingh KShaz BHNorberg PKAyasoufi KRailton COHotchkiss KMSampson JHfalseIL-7-mediated expansion of autologous lymphocytes increases CD8+ VLA-4 expression and accumulation in glioblastoma models.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 and2025-01-01T00:00:00Z2025 Jun2026-06-02T22:28:43.818Z2026-04-21T03:13:33.479ZS-EPMC121658024024470510.1172/JCI181471