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

By D. Singh, AP Ganesan, B Panwar, S Eschweiler, CJ Hanley, A Madrigal, C Ramírez-Suástegui, A Wang, J Clarke, O Wood, EM Garrido-Martin, SJ Chee, G Seumois, S Belanger, A Alzetani, E Woo, PS Friedmann, Shane Crotty, GJ Thomas, T Sanchez-Elsner, F Ay, CH Ottensmeier, P Vijayanand

Posted 09 Jan 2020
bioRxiv DOI: 10.1101/2020.01.08.898346

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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