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CD4+ follicular helper-like T cells are key players in anti-tumor immunity

CD4+ follicular helper-like T cells are key players in anti-tumor immunity
CD4+ follicular helper-like T cells are key players in anti-tumor immunity
To determine the nature of CD4+ T cells that provide ‘help’ for generating robust anti-tumor CD8+ cytotoxic T cell (CTL) responses, we profiled the transcriptomes of patient-matched CD4+ and CD8+ T cells present in the tumor micro-environment (TME) and analyzed them jointly using integrated weighted gene correlation network analysis. We found the follicular helper T cell (TFH) program in CD4+ T cells was strongly associated with proliferation and tissue-residency in CD8+ CTLs. Single-cell analysis demonstrated the presence of TFH-like cells and features linked to cytotoxic function and their provision of CD8+ T cell ‘help’. Tumor-infiltrating TFH-like cells expressed PD-1 and were enriched in tumors following checkpoint blockade, suggesting that they may respond to anti-PD-1 therapy. Adoptive transfer or induction of TFH cells in mouse models resulted in augmented CD8+ CTL responses and impairment of tumor growth, indicating an important role of TFH-like CD4+ T cells in anti-tumor immunity.
Singh, D.
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Ganesan, A.P.
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Panwar, B.
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Eschweiler, S.
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Hanley, C.J.
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Madrigal, A.
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Ramírez-Suástegui, C.
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Wang, A.
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Clarke, J.
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Wood, O.
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Garrido-Martin, E.M.
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Chee, S.J.
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Seumois, G.
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Belanger, S.
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Alzetani, A.
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Woo, E.
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Friedmann, P.S.
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Crotty, S.
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Thomas, G.J.
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Sanchez-Elsner, T.
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Ay, F.
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Ottensmeier, C.H.
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Vijayanand, P.
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Singh, D.
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Ganesan, A.P.
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Panwar, B.
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Eschweiler, S.
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Hanley, C.J.
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Madrigal, A.
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Ramírez-Suástegui, C.
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Wang, A.
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Clarke, J.
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Wood, O.
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Garrido-Martin, E.M.
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Chee, S.J.
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Seumois, G.
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Belanger, S.
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Alzetani, A.
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Woo, E.
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Friedmann, P.S.
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Crotty, S.
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Thomas, G.J.
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Sanchez-Elsner, T.
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Ay, F.
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Ottensmeier, C.H.
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Vijayanand, P.
79514f33-66cf-47cc-a8fa-46bbfc21b7d1

[Unknown type: UNSPECIFIED]

Record type: UNSPECIFIED

Abstract

To determine the nature of CD4+ T cells that provide ‘help’ for generating robust anti-tumor CD8+ cytotoxic T cell (CTL) responses, we profiled the transcriptomes of patient-matched CD4+ and CD8+ T cells present in the tumor micro-environment (TME) and analyzed them jointly using integrated weighted gene correlation network analysis. We found the follicular helper T cell (TFH) program in CD4+ T cells was strongly associated with proliferation and tissue-residency in CD8+ CTLs. Single-cell analysis demonstrated the presence of TFH-like cells and features linked to cytotoxic function and their provision of CD8+ T cell ‘help’. Tumor-infiltrating TFH-like cells expressed PD-1 and were enriched in tumors following checkpoint blockade, suggesting that they may respond to anti-PD-1 therapy. Adoptive transfer or induction of TFH cells in mouse models resulted in augmented CD8+ CTL responses and impairment of tumor growth, indicating an important role of TFH-like CD4+ T cells in anti-tumor immunity.

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Published date: 20 January 2020
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Identifiers

Local EPrints ID: 505173
URI: http://eprints.soton.ac.uk/id/eprint/505173
DOI: doi:10.1101/2020.01.08.898346
PURE UUID: 0005ecde-0428-48a1-8932-7f371f91bdd6
ORCID for P.S. Friedmann: ORCID iD orcid.org/0000-0003-3832-6607
ORCID for T. Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410
ORCID for P. Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

Catalogue record

Date deposited: 01 Oct 2025 16:40
Last modified: 02 Oct 2025 01:42

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Contributors

Author: D. Singh
Author: A.P. Ganesan
Author: B. Panwar
Author: S. Eschweiler
Author: C.J. Hanley
Author: A. Madrigal
Author: C. Ramírez-Suástegui
Author: A. Wang
Author: J. Clarke
Author: O. Wood
Author: E.M. Garrido-Martin
Author: S.J. Chee
Author: G. Seumois
Author: S. Belanger
Author: A. Alzetani
Author: E. Woo
Author: P.S. Friedmann ORCID iD
Author: S. Crotty
Author: G.J. Thomas
Author: T. Sanchez-Elsner ORCID iD
Author: F. Ay
Author: C.H. Ottensmeier
Author: P. Vijayanand ORCID iD

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