The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+follicular regulatory T cells in breast cancer

doi:10.21037/atm-21-3848

	The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+follicular regulatory T cells in breast cancer
	Miao, Xianyuan 1; Guo, Qiusheng 1; Pan, Zhiwen 2,3; Xu, Xiaohong 2,3; Shao, Xiying 3,4; Wang, Xiaojia 3,4
刊名	ANNALS OF TRANSLATIONAL MEDICINE
	2021-08-01
卷号	9
关键词	Breast cancer (BC) follicular regulatory T cell (Tfr) T-cell immunoglobulin mucin 3 (TIM-3)
ISSN号	2305-5839
DOI	10.21037/atm-21-3848
通讯作者	Shao, Xiying(shaoxy@zjcc.org.cn) ; Wang, Xiaojia(wxiaojia0803@163.com)
英文摘要	Background: Follicular regulatory T cells (Tfr) are a subset of regulatory T cells (Tregs) that suppress the humoral immune response in the germinal center. They are associated with increased rates of disease stabilization and decreased autoantibody levels in a variety of tumor and autoimmune diseases. The binding of T-cell immunoglobulin mucin 3 (TIM-3) and its ligand on the surface of Tfr cells could result in the depletion of T lymphocytes and the termination of the immune response mediated by helper T cell 1. However, the role of Tfr cells in breast cancer (BC) remains unclear. Methods: In this study, we detected the expression of CD4+CXCR5+Foxp3+Tfr cells in the peripheral blood of 35 BC patients and 30 healthy control patients by flow cytometry, and analyzed the relationship between Tfr cells and the clinical characteristics of patients. In addition, the expression of TIM-3 on the surface of Tfr cells in 6 triple-negative BC (TNBC) patients was further investigated using mass spectrometry. Results: We found a significant increase in Tfr cells in BC patients compared to healthy control patients (23.47%+/- 9.70% vs. 10.99%+/- 4.68%; P=0.001). Notably, the increase was more significant in early stage than advanced stage TNBC patients (28.52%+/- 10.75% vs. 18.69%+/- 5.19%; P=0.006), and there was a negative correlation between Tfr cells and serum lactate dehydrogenase (LDH) in early stage TNBC patients (r=-0.585; P=0.008). Additionally, we found that the expression of Tfr cells was higher in TNBC patients than luminal BC patients (28.25%+/- 10.11% vs. 18.5%+/- 8.15%; P=0.028); however, there was no significant difference in expression in hormone receptor positive (HR+) BC and hormone receptor negative (HR-) BC (P=0.141) patients. Notably, the surface of Tfr cells of TNBC patients had higher levels of TIM-3 expression than those of healthy control patients (3.93 +/- 0.92 vs. 2.65 +/- 0.15, respectively; t=-3.02; P<0.05), which the mass spectrometry showed were positively correlated with the intracellular Foxp3 expression of Tfr cells (r=0.82; P=0.036). Conclusions: Our results suggest that circulating Tfr cells and the expression of TIM-3 were significantly increased in BC patients, which were related to stage and histological type, and may be involved in the pathogenesis of BC.
资助项目	National Natural Science Foundation of China[81672597]
WOS关键词	TUMOR-INFILTRATING LYMPHOCYTES ; TRASTUZUMAB
WOS研究方向	Oncology ; Research & Experimental Medicine
语种	英语
出版者	AME PUBL CO
WOS记录号	WOS:000688281300001
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/125197]
专题	中国科学院合肥物质科学研究院
通讯作者	Shao, Xiying; Wang, Xiaojia
作者单位	1.Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou, Peoples R China 2.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Clin Lab, Hangzhou, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Med Oncol Breast Canc, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Miao, Xianyuan,Guo, Qiusheng,Pan, Zhiwen,et al. The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+follicular regulatory T cells in breast cancer[J]. ANNALS OF TRANSLATIONAL MEDICINE,2021,9.
APA	Miao, Xianyuan,Guo, Qiusheng,Pan, Zhiwen,Xu, Xiaohong,Shao, Xiying,&Wang, Xiaojia.(2021).The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+follicular regulatory T cells in breast cancer.ANNALS OF TRANSLATIONAL MEDICINE,9.
MLA	Miao, Xianyuan,et al."The characteristics and novel clinical implications of CD4+CXCR5+Foxp3+follicular regulatory T cells in breast cancer".ANNALS OF TRANSLATIONAL MEDICINE 9(2021).