2. Academic Validation
  3. Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells

Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells

  • Signal Transduct Target Ther. 2020 Apr 29;5(1):41. doi: 10.1038/s41392-020-0129-7.
Chao Ni  # 1 2 3,  Qing-Qing Fang  # 4,  Wu-Zhen Chen  # 5 6,  Jin-Xing Jiang 5 6,  Zhou Jiang 5,  Jun Ye 6,  Ting Zhang 6,  Liu Yang 4,  Fan-Bo Meng 7,  Wen-Jie Xia 8,  Miaochun Zhong 8,  Jian Huang 9 10
Affiliations

Affiliations

  • 1 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China. [email protected].
  • 2 Key Laboratory of Tumour Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China. [email protected].
  • 3 Key Laboratory of Tumour Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China. [email protected].
  • 4 Key Laboratory of Tumour Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
  • 5 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
  • 6 Key Laboratory of Tumour Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
  • 7 Department of Thyroid and Breast Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, 312099, China.
  • 8 Department of Thyroid and Breast Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
  • 9 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China. [email protected].
  • 10 Key Laboratory of Tumour Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, China. [email protected].
  • # Contributed equally.
PMID: 32345959 DOI: 10.1038/s41392-020-0129-7
Abstract

γδT cells have been reported to exert immunosuppressive functions in multiple solid malignant diseases, but their immunosuppressive functional subpopulation in breast Cancer (BC) is still undetermined. Here, we collected 40 paired BC and normal tissue samples from Chinese patients for analysis. First, we showed that γδT1 cells comprise the majority of CD3+ T cells in BC; next, we found that CD73+γδT1 cells were the predominant regulatory T-cell (Treg) population in BC, and that their prevalence in peripheral blood was also related to tumour burden. In addition, CD73+γδT1 cells exert an immunosuppressive effect via adenosine generation. We also found that BC could modulate CD73 expression on γδT cells in a non-contact manner. The microarray analysis and functional experiments indicated that breast tumour cell-derived exosomes (TDEs) could transmit lncRNA SNHG16, which upregulates CD73 expression, to Vδ1 T cells. Regarding the mechanism, SNHG16 served as a ceRNA by sponging miR-16-5p, which led to the derepression of its target gene SMAD5 and resulted in potentiation of the TGF-β1/SMAD5 pathway to upregulate CD73 expression in Vδ1 T cells. Our results showed that the BC-derived exosomal SNHG16/miR-16-5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation, thus inducing CD73 expression in Vδ1 T cells. Our results first identify the significance of CD73+Vδ1 Tregs in BC, and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.

Figures
Products