Back to Search
Start Over
Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4+CD25+Foxp3+ regulatory T cells.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2012 Sep; Vol. 92 (3), pp. 673-82. Date of Electronic Publication: 2012 May 25. - Publication Year :
- 2012
-
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.
- Subjects :
- Coculture Techniques
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Forkhead Transcription Factors immunology
Humans
Interleukin-2 Receptor alpha Subunit immunology
Monocytes immunology
Breast Neoplasms immunology
Dendritic Cells immunology
Lymphocyte Activation immunology
T-Lymphocytes, Regulatory immunology
Tumor Escape immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 92
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 22636320
- Full Text :
- https://doi.org/10.1189/jlb.0112048