biostudies-literatureZhao QNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health735https://www.ebi.ac.uk/biostudies/studies/S-EPMC9911733biostudies-literatureUnknown14(1)Although tissue-resident memory T (T_RM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain T_RM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)-specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8⁺ T_RM cells that prevent glioblastoma recurrence. These CD8⁺ T_RM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8⁺ T_RM cells reject glioma cells. MechanisticNature communicationsFGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells.PMC9911733R01 CA200574Xia XKong LYan JHeimberger ABFowlkes NWJiang SWang JLi SHu JYi SFZhao QTian XDao LHHashizume RJia ZMasopust DfalseFGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells.Although tissue-resident memory T (T_RM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain T_RM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)-specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8⁺ T_RM cells that prevent glioblastoma recurrence. These CD8⁺ T_RM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8⁺ T_RM cells reject glioma cells. Mechanistic2023-01-01T00:00:00Z2023 Feb2025-06-01T04:00:55.371Z2025-06-01T04:00:55.371ZS-EPMC99117333675951710.1038/s41467-023-36430-2