| First Author | Chaurio RA | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 1 | Pages | 115-128.e9 |
| PubMed ID | 35021053 | Mgi Jnum | J:335798 |
| Mgi Id | MGI:6874632 | Doi | 10.1016/j.immuni.2021.12.007 |
| Citation | Chaurio RA, et al. (2022) TGF-beta-mediated silencing of genomic organizer SATB1 promotes Tfh cell differentiation and formation of intra-tumoral tertiary lymphoid structures. Immunity 55(1):115-128.e9 |
| abstractText | 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 CD4(Cre)Satb1(f/f) mice enriched for antigen-specific Tfh cells, and TGF-beta-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 CD4(Cre)Satb1(f/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-beta-mediated silencing of Satb1 licenses Tfh cell differentiation, providing insight into the genesis of TLS within tumors. |
