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Publication : FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells.

First Author  Zhao Q Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  735
PubMed ID  36759517 Mgi Jnum  J:336335
Mgi Id  MGI:7433691 Doi  10.1038/s41467-023-36430-2
Citation  Zhao Q, et al. (2023) FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells. Nat Commun 14(1):735
abstractText  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-alphaFGL2) 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 naive mice, these CD8(+) T(RM) cells reject glioma cells. Mechanistically, T-alphaFGL2 cell treatment increased the number of CD69(+)CD8(+) brain-resident memory T cells in tumor-bearing mice via a CXCL9/10 and CXCR3 chemokine axis. These findings suggest that tumor-specific brain-resident CD8(+) T(RM) cells may have promising implications for the prevention of brain tumor recurrence.
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