Enrichment of CCR6+Foxp3+ regulatory T cells in the tumor mass correlates with impaired CD8+ T cell function and poor prognosis of breast cancer.
CCR6(+) subset of CD4(+) regulatory T cells, a newly characterized subset of Tregs, has been reported to contribute to local immune inhibition. However, whether CCR6(+) Tregs are present in tumor environment and their relation to the prognosis of tumor remain to be elucidated. In this study, we found that CCR6(+) CD4(+) CD25(high) Tregs, expressing high levels of CD45RO, are dominantly enriched in tumor mass from patients with breast cancer. Furthermore, the frequency of CCR6(+) Tregs, but not CCR6(-) Tregs in tumor infiltrating lymphocytes (TILs), significantly increased in patients during tumor progression, which reversely correlated with decreased frequency of the IFN-gamma(+)CD8(+)T cells in TILs. Most importantly, the frequency of CCR6(+) Tregs, but not CCR6(-) Tregs, reversely correlated to the survival of patients with breast cancer. This study suggested that a new subset of tumor-resident Tregs, CCR6(+) Tregs, may be dominantly responsible for the immunosuppression in tumor immunity and a potential predictor of the poor prognosis of breast cancer.
Xu
Lin
L
Institute for Immunobiology and Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, PR China.
Xu
Wei
W
Qiu
Shenglong
S
Xiong
Sidong
S
D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009367:Neoplasm Staging; D011379:Prognosis; D054399:Receptors, CCR6 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C106311:CCR6 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054399:Receptors, CCR6