PT  - JOURNAL ARTICLE
AU  - D Singh
AU  - AP Ganesan
AU  - B Panwar
AU  - S Eschweiler
AU  - CJ Hanley
AU  - A Madrigal
AU  - C Ramírez-Suástegui
AU  - A Wang
AU  - J Clarke
AU  - O Wood
AU  - EM Garrido-Martin
AU  - SJ Chee
AU  - G Seumois
AU  - S Belanger
AU  - A Alzetani
AU  - E Woo
AU  - PS Friedmann
AU  - S Crotty
AU  - GJ Thomas
AU  - T Sanchez-Elsner
AU  - F Ay
AU  - CH Ottensmeier
AU  - P Vijayanand
TI  - CD4<sup>+</sup> follicular helper-like T cells are key players in anti-tumor immunity
AID  - 10.1101/2020.01.08.898346
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.08.898346
4099  - http://biorxiv.org/content/early/2020/01/09/2020.01.08.898346.short
4100  - http://biorxiv.org/content/early/2020/01/09/2020.01.08.898346.full
AB  - 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.