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The immunosuppressive microenvironment in cancer: local and systemic effects on patients monocytes.

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Author(s):
Rodrigo Nalio Ramos
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas
Defense date:
Examining board members:
Jose Alexandre Marzagao Barbuto; Christophe Caux; Yves Delneste; Charles Dumontet; Ana Paula Lepique; Luiz Rodolpho Raja Gabaglia Travassos
Advisor: Jose Alexandre Marzagao Barbuto
Abstract

Cancer development is associated with failures in the immune system. We investigated here if breast tumor microenvironment affect the differentiation of monocytes. We observed that the high frequency of macrophages (MΦ) CD163+ was associated with poor patients survival and a low infiltration of CD3+ T cells in tumors. Supernatants obtained from dilacerated tumors (SNDil) skewed the differentiation of monocytes into CD163highIL10high MΦ, which suppressed CD4+ T cells. The CD163highIL-10high phenotype was associated with high levels of M-CSF, TGF-β and VEGF in tumors. Circulating monocytes from patients failed to differentiate into M1-MΦ; gave rise to DCs able to induce high frequency of regulatory T cells (Tregs) and produced high levels of anti-inflammatory cytokines under LPS activation. In conclusion, the tumor microenvironment promotes the differentiation of suppressive CD163highIL10high MΦ and affects the potential of differentiation of patients\' monocytes systemically. (AU)

FAPESP's process: 11/08905-7 - Study of mechanisms involved in modulation of T lymphocyte response against tumor antigens by dendritic cells derived from cancer patients monocytes
Grantee:Rodrigo Nalio Ramos
Support type: Scholarships in Brazil - Doctorate