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

Qingnan Zhao, Jiemiao Hu, Lingyuan Kong, Shan Jiang, Xiangjun Tian, Jing Wang, Rintaro Hashizume, Zhiliang Jia, Natalie Wall Fowlkes, Jun Yan, Xueqing Xia, Sofia F. Yi, Long Hoang Dao, David Masopust, Amy B. Heimberger and Shulin Li ()
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Qingnan Zhao: Shanghai Jiao Tong University School of Medicine
Jiemiao Hu: The University of Texas MD Anderson Cancer Center
Lingyuan Kong: The University of Texas MD Anderson Cancer Center
Shan Jiang: Columbia University Irving Medical Center
Xiangjun Tian: The University of Texas MD Anderson Cancer Center
Jing Wang: The University of Texas MD Anderson Cancer Center
Rintaro Hashizume: Northwestern University
Zhiliang Jia: The University of Texas MD Anderson Cancer Center
Natalie Wall Fowlkes: The University of Texas MD Anderson Cancer Center
Jun Yan: Capital Medical University
Xueqing Xia: The University of Texas MD Anderson Cancer Center
Sofia F. Yi: The University of Texas MD Anderson Cancer Center
Long Hoang Dao: The University of Texas MD Anderson Cancer Center
David Masopust: University of Minnesota
Amy B. Heimberger: The University of Texas MD Anderson Cancer Center
Shulin Li: The University of Texas MD Anderson Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM 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+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM 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+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 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+ TRM cells may have promising implications for the prevention of brain tumor recurrence.

Date: 2023
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DOI: 10.1038/s41467-023-36430-2

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