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, Shulin Li

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number735
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Funding Information:
We appreciate Editing Services, Research Medical Library at MD Anderson for helping us edit our manuscript. This research used the Flow Cytometry, Cellular Imaging Facility and DNA Analysis Core Facility and Monoclonal Antibody Core Facility at MD Anderson, which are supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant P30 CA016672. This work was supported by National Institutes of Health Grants R01CA203493, NIH/NCI (S.L. and A.H.) and R01NS122857, NIH/NINDS (S.L. and A.H.).

Publisher Copyright:
© 2023, The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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