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Composition and plasticity of triple‐negative breast carcinoma‐infiltrating regulatory T cells.
- Source :
-
APMIS . Mar2020, Vol. 128 Issue 3, p260-269. 10p. - Publication Year :
- 2020
-
Abstract
- Low Foxp3+ regulatory T‐cell (Treg) presence in the tumor‐infiltrating lymphocytes (TILs) is considered favorable in breast cancer, and numerous CD25‐targeting agents have been applied in the attempt to remove Foxp3+ Treg cells, which typically present CD4+CD25+/hi surface phenotype. However, CD25 is not Treg‐exclusive and can be upregulated by effector T cells. Hence, CD25 depletion may cause the elimination of activated T cells that are responding to tumor‐specific antigens. In this study, the composition and function of CD4+CD25+ cells inside the microenvironment of triple‐negative breast carcinoma (TNBC) were investigated. Directly ex vivo, the Foxp3+ Treg cells represented a minor subset in total CD4+CD25+ TILs. Significant differences were observed in the expression of Treg‐associated molecules between CD4+CD25+Foxp3+ TILs and CD4+CD25+Foxp3− TILs. While both the CD4+CD25+Foxp3+ and the CD4+CD25+Foxp3− TILs could express CTLA‐4 and LAG‐3, the expression levels were significantly higher in CD4+CD25+Foxp3+ TILs than in CD4+CD25+Foxp3− TILs. Upon TCR stimulation, the expression of TGF‐beta was significantly higher in CD4+CD25+Foxp3+ TILs, while the expression of IL‐10 was significantly higher in CD4+CD25+Foxp3− TILs. These differences were conserved in the blood counterparts of these cells. Interestingly, the level of CD25+Foxp3+ cells in circulating CD4+ T cells was positively correlated with the level of CD25+Foxp3+ cells in CD4+ TILs, but the level of CD25+Foxp3− cells in circulating CD4+ T cells was not associated with the level of CD25+Foxp3‐ cells in CD4+ TILs. Th17‐polarizing medium could readily remodel CD4+CD25+Foxp3−, but not CD4+CD25+Foxp3+, T cells into RORgammat and IL‐17‐expressing T cells, demonstrating stronger plasticity of the former subset. Together, these data demonstrated that the CD4+CD25+ TILs were composed of distinctive Foxp3− and Foxp3+ cells, with the former representing the major subset. The antigen specificity and effector molecule expression of the CD4+CD25+Foxp3− thus require further analyses. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SUPPRESSOR cells
*BLOOD cells
*BREAST
*CELL physiology
Subjects
Details
- Language :
- English
- ISSN :
- 09034641
- Volume :
- 128
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- APMIS
- Publication Type :
- Academic Journal
- Accession number :
- 143170541
- Full Text :
- https://doi.org/10.1111/apm.13022