DENDRITIC CELLS FUNCTION DISABILITY PROMOTED BY CANCER MIGHT BEGIN AT THEIR HEMATOPOIETIC PRECURSORS

• Grant number: 12/17643-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2013
• End date: March 22, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Ana Carolina Franco Ferreira
• 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
• Associated scholarship(s): 14/14302-1 - NF-kB Promoter-Recruitment in dendritic cell differentiation - possible modulation by tumour cells, BE.EP.PD

Abstract

Dendritic cells (DCs) are highly efficient antigen-presenting cells that show functional disability in cancer patients. This phenomenon may be an important tumor escape mechanism, since functional modification of DCs can prevent the development of an effective immune response against tumors. Therefore, any attempt to induce an immune response against tumors should take into account such deficiency and, ideally, correct it. Interestingly, DCs that are generated in vitro, derived from cancer patients' precursors, also have these deficiencies, indicating a systemic effect of cancer on DC precursors. The understanding of the tumors´ molecular mechanisms of action on immune response through DC, as well as knowing when it occurs in the hematopoietic pathway, is essential for a more efficient use of cancer immunotherapeutic treatments. In this context, the family of nuclear factor kappa-B (NF-kB) is a fundamental target of research, since it is involved in DCs differentiation and maturation. Thus, the objective of this project is to evaluate the influence of tumors on in vitro DC differentiation from monocytes or CD34+ hematopoietic progenitor cells (HPC), also evaluating the role of NF-kB in this process. With this purpose, myelomonocytic lineages will be co-cultured with tumor cell lines and the effect of this setting on the myelomonocytic cells and their differentiation into DCs will be evaluated. We also intend to use genetic engineering techniques to try to minimize / reverse the alterations observed.