| Autor: |
Roger Li, Kimberly B. Sprenger, John R. Robinson, Carmen M. Anadon, Bradford A. Perez, Jose R. Conejo-Garcia, Antonio C. Ortiz, Jessica A. Mine, Sneak Peek Administrator, Subir Biswas, John J. Powers, Gunjan Mandal, Sumit Mehta, Tara Lee Costich, Kyle K. Payne, Alexandra Martin, Xiaoqing Yu, Pasquale P. Innamarato, Carlos Moran, Carly M. Harro, Jodi L. Kroeger, Tyler J. Curiel, Paulo C. Rodriguez, Zhitao Wang, Ricardo A. Chaurio, Kristen E. Rigolizzo |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| Popis: |
Tertiary Lymphoid Structures (TLS) are commonly identified in human tumors with improved outcome, but how they are orchestrated remains elusive. We show that ablation of the genomic organizer SATB1 triggers the polarization of CD4+ T-cells into antigen-specific T Follicular Helper (TFH) cells. In contrast, SATB1 expression is required for conversion of CD4+ T-cells into induced regulatory T-cells (Treg), including T Follicular Regulatory (TFR) cells. Paradoxically, Tgf-β-driven Satb1 silencing causes Icos de-repression and prevents TFR differentiation, driving TFH polarization and increased isotype-switched B cell responses. Tumors in mice carrying Satb1-deficient CD4+ T-cells accumulate more tumor antigen-specific, Light/Cxcl13/Il-21-producing TFH cells, causing germinal center formation and spontaneous TLS assembly, which antagonizes tumor growth. Accordingly, TFH cell transfer induces large TLS within orthotopic ovarian tumors. Therefore, SATB1 repression in CD4+ T-cells licenses TFH cell differentiation while preventing Treg conversion, a central mechanism during TLS assembly that can be exploited to boost anti-tumor immunity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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