STAT3 inhibition by thymosin alpha-1: Effective strategy for the functional recovery of cancer patients" monocyte-derived dendritic cells?

• Grant number: 11/15371-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Cristiano Jacob de Moraes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach, AP.TEM

Abstract

Efficient initiation, activation and coordination of adaptive immune responses, orchestred by dendritic cells (DCs), is the main mechanism responsible for the development of anti-tumoral immunity. However, it is known that cancer uses a wide range of suppressor mechanisms to evade the immune response and to develop in imunocompetent individuals.Tumors establish an environment unfavorable to the immune response mainly by the production of soluble factors such as VEGF, IL-10, IL-6 and TGF-beta and by the expression of negative membrane co-stimuli, such as PD-L1 and PD -L2,all of which create an immunosuppressive microenvironment within the tumor. Such phenomena influence also DC phenotype and function, since data in the literature describe DCs of patients with cancer as dysfunctional and anergic to stimulate and /or modulate lymphocyte responses.Among the various strategies used to modulate DC function, the thymic hormone, thymosin-alpha1 was shown to activate these cells, inducing increased expression of CD80, CD86 and MHC class II molecules. In parallel, data from our laboratory show that this hormone can cause a decreased expression of PD-L1 in cancer patients monocyte-derived DCs. It is known that this molecule has its expression regulated by the transcription factor STAT-3, so the aim of this work is to investigate if thymosin-±1 is able to inhibit the activation of STAT-3, and thus restore functionaly cancer patients" DCs.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MORAES, Cristiano Jacob de. Effects of tymosin alpha 1 and inhibition of STAT-3 in monocyte-derived dendritic cells.. 2013. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.