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-α, 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-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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Ramos RN,Chin LS,Dos Santos AP,Bergami-Santos PC,Laginha F,Barbuto JAdoi
10.1189/jlb.0112048subject
Has Abstractpub_date
2012-09-01 00:00:00pages
673-82issue
3eissn
0741-5400issn
1938-3673pii
jlb.0112048journal_volume
92pub_type
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