Cargando…

FGL2-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-li...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Qingnan, Hu, Jiemiao, Kong, Lingyuan, Jiang, Shan, Tian, Xiangjun, Wang, Jing, Hashizume, Rintaro, Jia, Zhiliang, Fowlkes, Natalie Wall, Yan, Jun, Xia, Xueqing, Yi, Sofia F., Dao, Long Hoang, Masopust, David, Heimberger, Amy B., Li, Shulin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911733/
https://www.ncbi.nlm.nih.gov/pubmed/36759517
http://dx.doi.org/10.1038/s41467-023-36430-2
_version_ 1784885053657972736
author Zhao, Qingnan
Hu, Jiemiao
Kong, Lingyuan
Jiang, Shan
Tian, Xiangjun
Wang, Jing
Hashizume, Rintaro
Jia, Zhiliang
Fowlkes, Natalie Wall
Yan, Jun
Xia, Xueqing
Yi, Sofia F.
Dao, Long Hoang
Masopust, David
Heimberger, Amy B.
Li, Shulin
author_facet Zhao, Qingnan
Hu, Jiemiao
Kong, Lingyuan
Jiang, Shan
Tian, Xiangjun
Wang, Jing
Hashizume, Rintaro
Jia, Zhiliang
Fowlkes, Natalie Wall
Yan, Jun
Xia, Xueqing
Yi, Sofia F.
Dao, Long Hoang
Masopust, David
Heimberger, Amy B.
Li, Shulin
author_sort Zhao, Qingnan
collection PubMed
description 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. 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(+) T(RM) cells may have promising implications for the prevention of brain tumor recurrence.
format Online
Article
Text
id pubmed-9911733
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-99117332023-02-11 FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells Zhao, Qingnan Hu, Jiemiao Kong, Lingyuan Jiang, Shan Tian, Xiangjun Wang, Jing Hashizume, Rintaro Jia, Zhiliang Fowlkes, Natalie Wall Yan, Jun Xia, Xueqing Yi, Sofia F. Dao, Long Hoang Masopust, David Heimberger, Amy B. Li, Shulin Nat Commun Article 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. 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(+) T(RM) cells may have promising implications for the prevention of brain tumor recurrence. Nature Publishing Group UK 2023-02-10 /pmc/articles/PMC9911733/ /pubmed/36759517 http://dx.doi.org/10.1038/s41467-023-36430-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhao, Qingnan
Hu, Jiemiao
Kong, Lingyuan
Jiang, Shan
Tian, Xiangjun
Wang, Jing
Hashizume, Rintaro
Jia, Zhiliang
Fowlkes, Natalie Wall
Yan, Jun
Xia, Xueqing
Yi, Sofia F.
Dao, Long Hoang
Masopust, David
Heimberger, Amy B.
Li, Shulin
FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title_full FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title_fullStr FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title_full_unstemmed FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title_short FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells
title_sort fgl2-targeting t cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911733/
https://www.ncbi.nlm.nih.gov/pubmed/36759517
http://dx.doi.org/10.1038/s41467-023-36430-2
work_keys_str_mv AT zhaoqingnan fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT hujiemiao fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT konglingyuan fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT jiangshan fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT tianxiangjun fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT wangjing fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT hashizumerintaro fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT jiazhiliang fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT fowlkesnataliewall fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT yanjun fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT xiaxueqing fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT yisofiaf fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT daolonghoang fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT masopustdavid fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT heimbergeramyb fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells
AT lishulin fgl2targetingtcellsexhibitantitumoreffectsonglioblastomaandrecruittumorspecificbrainresidentmemorytcells