| Literature DB >> 35021053 |
Ricardo A Chaurio1, Carmen M Anadon1, Tara Lee Costich1, Kyle K Payne1, Subir Biswas1, Carly M Harro1, Carlos Moran2, Antonio C Ortiz3, Carla Cortina1, Kristen E Rigolizzo1, Kimberly B Sprenger1, Jessica A Mine1, Patrick Innamarato1, Gunjan Mandal1, John J Powers1, Alexandra Martin4, Zhitao Wang1, Sumit Mehta4, Bradford A Perez5, Roger Li6, John Robinson7, Jodi L Kroeger7, Tyler J Curiel8, Xiaoqing Yu9, Paulo C Rodriguez1, Jose R Conejo-Garcia10.
Abstract
The immune checkpoint receptor PD-1 on T follicular helper (Tfh) cells promotes Tfh:B cell interactions and appropriate positioning within tissues. Here, we examined the impact of regulation of PD-1 expression by the genomic organizer SATB1 on Tfh cell differentiation. Vaccination of CD4CreSatb1f/f mice enriched for antigen-specific Tfh cells, and TGF-β-mediated repression of SATB1 enhanced Tfh differentiation of human T cells. Mechanistically, high Icos expression in Satb1-/- CD4+ T cells promoted Tfh cell differentiation by preventing T follicular regulatory cell skewing and resulted in increased isotype-switched B cell responses in vivo. Ovarian tumors in CD4CreSatb1f/f mice accumulated tumor antigen-specific, LIGHT+CXCL13+IL-21+ Tfh cells and tertiary lymphoid structures (TLS). TLS formation decreased tumor growth in a CD4+ T cell and CXCL13-dependent manner. The transfer of Tfh cells, but not naive CD4+ T cells, induced TLS at tumor beds and decreased tumor growth. Thus, TGF-β-mediated silencing of Satb1 licenses Tfh cell differentiation, providing insight into the genesis of TLS within tumors.Entities:
Keywords: B cell cancer; SATB1; T follicular helper cell; immuno-oncology; tertiary lymphoid structure; tumor immunology
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Year: 2022 PMID： 35021053 PMCID： PMC8852221 DOI： 10.1016/j.immuni.2021.12.007
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474