Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4(+)CD25(+)Foxp3(+) regulatory T cells

Author(s)

Ramos, Rodrigo Nalio ; Chin, Lilian Sally ; dos Santos, Ana Paula S. A. ^[1] ; Bergami-Santos, Patricia Cruz ; Laginha, Fabio ^[2] ; Barbuto, Jose Alexandre M. ^[3]

Affiliation

^[1] Univ Fed Maranhao, Dept Physiol, Ma - Brazil

^[2] Perola Byngton Hosp, Dept Radiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Lab Tumor Immunol, Dept Immunol, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Leukocyte Biology; v. 92, n. 3, p. 673-682, SEP 2012.
• Web of Science Citations: 38

Abstract

DCs orchestrate immune responses contributing to the pattern of response developed. In cancer, DCs may play a dysfunctional role in the induction of CD4(+)CD25(+) Foxp3(+) Tregs, contributing to immune evasion. We show here that Mo-DCs from breast cancer patients show an altered phenotype and induce preferentially Tregs, a phenomenon that occurred regardless of DC maturation stimulus (sCD40L, cytokine cocktail, TNF-alpha, and LPS). The Mo-DCs of patients induced low proliferation of allogeneic CD3(+)CD25(neg)Foxp3(neg) cells, which after becoming CD25(+), suppressed mitogen-stimulated T cells. Contrastingly, Mo-DCs from healthy donors induced a stronger proliferative response, a low frequency of CD4(+)CD25(+)Foxp3(+) with no suppressive activity. Furthermore, healthy Mo-DCs induced higher levels of IFN-gamma, whereas the Mo-DCs of patients induced higher levels of bioactive TGF-beta 1 and IL-10 in cocultures with allogeneic T cells. Interestingly, TGF-beta 1 blocking with mAb in cocultures was not enough to completely revert the Mo-DCs of patients' bias toward Treg induction. Altogether, these findings should be considered in immunotherapeutic approaches for cancer based on Mo-DCs. J. Leukoc. Biol. 92: 673-682; 2012. (AU)

• FAPESP's process: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach
• Grantee: Jose Alexandre Marzagão Barbuto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/02074-6 - Investigation of a possible immunossuppressive bias in monocyte-derived dendritic cells from cancer patients
• Grantee: Rodrigo Nalio Ramos
• Support Opportunities: Scholarships in Brazil - Master