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

by Ganesan, Anusha Preethi , Panwar, Bharat , Crotty, Shane , Sanchez-Elsner, Tilman , Ay, Ferhat , Pandurangan Vijayanand , Wang, Alice , Ciro Ramirez Suastegui , Clarke, James , Belanger, Simon , Ottensmeier, Christian , Madrigal, Ariel , Friedmann, Peter , Eschweiler, Simon , Wood, Oliver , Thomas, Gareth , Chee, Serena , Singh, Divya , Alzetani, Aiman , Seumois, Gregory , Garrido-Martin, Eva Maria , Hanley, Chris , Woo, Edwin

in Adoptive transfer / Animal models / CD4 antigen / CD8 antigen / Cell culture / Cell proliferation / Cytotoxicity / Immune checkpoint / Immunology / Lymphocytes / Lymphocytes T / PD-1 protein

2020

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

in Adoptive transfer / Animal models / CD4 antigen / CD8 antigen / Cell culture / Cell proliferation / Cytotoxicity / Immune checkpoint / Immunology / Lymphocytes / Lymphocytes T / PD-1 protein

2020

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

in Adoptive transfer / Animal models / CD4 antigen / CD8 antigen / Cell culture / Cell proliferation / Cytotoxicity / Immune checkpoint / Immunology / Lymphocytes / Lymphocytes T / PD-1 protein

2020

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Paper

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

Ganesan, Anusha Preethi,

Panwar, Bharat,

Crotty, Shane,

Sanchez-Elsner, Tilman,

Ay, Ferhat,

Pandurangan Vijayanand,

Wang, Alice,

Ciro Ramirez Suastegui,

Clarke, James,

Belanger, Simon,

Ottensmeier, Christian,

Madrigal, Ariel,

Friedmann, Peter,

Eschweiler, Simon,

Wood, Oliver,

Thomas, Gareth,

Chee, Serena,

Singh, Divya,

Alzetani, Aiman,

Seumois, Gregory,

Garrido-Martin, Eva Maria,

Hanley, Chris,

Woo, Edwin

2020

Overview

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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Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

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