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

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Singh, D, Ganesan, AP, Panwar, B, Eschweiler, S, Hanley, CJ ORCID: 0000-0003-3816-7220, Madrigal, A, Ramírez-Suástegui, C, Wang, A, Clarke, J, Wood, O et al (show 13 more authors) , Garrido-Martin, EM ORCID: 0000-0002-8094-2668, Chee, SJ, Seumois, G, Belanger, S, Alzetani, A, Woo, E, Friedmann, PS ORCID: 0000-0003-3832-6607, Crotty, S, Thomas, GJ, Sanchez-Elsner, T ORCID: 0000-0003-1915-2410, Ay, F ORCID: 0000-0002-0708-6914, Ottensmeier, CH ORCID: 0000-0003-3619-1657 and Vijayanand, P (2020) CD4⁺follicular helper-like T cells are key players in anti-tumor immunity. Journal of Clinical Investigation. 2020.01.08.898346-. ISSN 0021-9738

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Abstract

<h4>ABSTRACT</h4> 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 (T FH ) program in CD4 + T cells was strongly associated with proliferation and tissue-residency in CD8 + CTLs. Single-cell analysis demonstrated the presence of T FH -like cells and features linked to cytotoxic function and their provision of CD8 + T cell ‘help’. Tumor-infiltrating T FH -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 T FH cells in mouse models resulted in augmented CD8 + CTL responses and impairment of tumor growth, indicating an important role of T FH -like CD4 + T cells in anti-tumor immunity.

Item Type:	Article
Uncontrolled Keywords:	32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, 3204 Immunology, Cancer, Immunotherapy, 2.1 Biological and endogenous factors
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	22 Dec 2021 09:20
Last Modified:	24 Oct 2025 12:54
DOI:	10.1101/2020.01.08.898346
Open Access URL:	https://www.biorxiv.org/content/10.1101/2020.01.08...
Related Websites:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3145818