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

Singh, D.; Ganesan, A. P.; Panwar, B.; Eschweiler, S.; Hanley, C.; Madrigal, A.; Ramirez Suastegui, C.; Wang, A.; Clarke, J.; Wood, O.; Garrido-Martin, E. M.; Chee, S.; Seumois, G.; Belanger, S.; Alzetani, A.; Woo, E.; Friedmann, P.; Crotty, S.; Thomas, G.; Sanchez-Elsner, T.; Ay, F.; Ottensmeier, C.; Vijayanand, P.

doi:10.1101/2020.01.08.898346

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bioRxiv · 10.1101/2020.01.08.898346

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

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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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Singh, D., Ganesan, A. P., Panwar, B., Eschweiler, S., Hanley, C., Madrigal, A., Ramirez Suastegui, C., Wang, A., Clarke, J., Wood, O., Garrido-Martin, E. M., Chee, S., Seumois, G., Belanger, S., Alzetani, A., Woo, E., Friedmann, P., Crotty, S., Thomas, G., Sanchez-Elsner, T., Ay, F., Ottensmeier, C., Vijayanand, P.. 2020-01-09. CD4+ follicular helper-like T cells are key players in anti-tumor immunity. https://doi.org/10.1101/2020.01.08.898346

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