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| Author(s): |
Patrícia Argenta Toniolo
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2014-09-23 |
| Examining board members: |
Jose Alexandre Marzagao Barbuto;
Karina Ramalho Bortoluci;
Jean Pierre Schatzmann Peron;
Elaine Guadelupe Rodrigues;
Deborah Schechtman
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| Advisor: | Jose Alexandre Marzagao Barbuto |
| Abstract | |
Discovery of new targets to reverse tumor immunosuppression on dendritic cells (DCs) hold great therapeutic promise. Here, we identify that monocytes from chronic lymphocytic leukemia (CLL) patients have alteration in IL-4-induced STAT6 signaling that prevents DCs phenotypic and functional maturation. Although patients monocytes display high IL-4R expression, STAT6 activity is inhibited because of elevated SOCS5 levels. IL-10-treatment of healthy donors monocytes reproduces this altered mechanism (STAT6/SOCS5) and leads to a defective DC differentiation. These findings indicate that a high SOCS5 level is involved on CLL-DCs impaired function. Moreover, we find that pharmacologic inhibition of STAT3 by pyrimethamine, a clinical trial compound for CLL, does not affect LPS-induced DCs maturation while STAT5 inhibition by JQ1 prevents it. Our findings show that STAT5 is important for DCs maturation, and suggest that JQ1, but not pyrimetamine, can cause immunosuppression. Additionally, SOCS5 emerges as a new potential target for cancer treatment. (AU) | |
| FAPESP's process: | 10/15312-0 - Suppressors of cytokines signaling (SOCS) in the functional modulation of dendritic cells derived from patients with cancer |
| Grantee: | Patricia Argenta Toniolo |
| Support Opportunities: | Scholarships in Brazil - Doctorate |