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

Journal of Leukocyte Biology

Ana Paula S. A. dos Santos²  FÃbio Laginha and¹  Rodrigo Nalio Ramos³  Patrícia Cruz Bergami-Santos³  José Alexandre M. Barbuto³  Lilian Sally Chin³ 

[1] Department of Radiology, Perola Byngton Hospital, Sao Paulo, SP, Brazil Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;  Department of Physiology, Federal University of Maranhao, MA, Brazil;Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;

关键词: cancer;    tumor immunology;    tolerance;   

DOI  :  10.1189/jlb.0112048

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-α, and LPS). The Mo-DCs of patients induced low proliferation of allogeneic CD3+CD25negFoxp3neg 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-γ, whereas the Mo-DCs of patients induced higher levels of bioactive TGF-β1 and IL-10 in cocultures with allogeneic T cells. Interestingly, TGF-β1 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.

【 授权许可】

Unknown