The Different T-cell Receptor Repertoires in Breast Cancer Tumors, Draining Lymph Nodes, and Adjacent Tissues.

Abstract

T lymphocytes infiltrate the microenvironment of breast cancer tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCR) borne by T cells within tumors, in the surrounding tissues, and in draining lymph nodes are largely unexplored in human breast cancer. Consequently, information about the relative extent of possible T-cell exchange between these tissues is also lacking. Here, we have analyzed the TCR repertoire of T cells using multiplex PCR and high-throughput sequencing of the TCRβ chain in the tissues of tumor, adjacent nontumor, and axillary lymph nodes of breast cancer patients. T-cell repertoire diversity in tumors was lower than in lymph nodes, but higher than in nontumor tissue, with a preferential use of variable and joining genes. These data are consistent with the hypothesis that most of the T cells in tumors derive from the lymph node, followed by their expansion in tumor tissue. Positive nodes appeared to enhance T-cell infiltration into tumors and T-cell clonal expansion in lymph nodes. Additionally, the similarity in TCR repertoire between tumor and nontumor tissue was significantly higher in luminal-like, rather than basal-like, breast cancer. Our study elucidated the high heterogeneity of the TCR repertoire and provides potential for future improvements in immune-related diagnosis, therapy, and prognosis for breast cancer patients. Cancer Immunol Res; 5(2); 148-56. ©2016 AACR.

• Authors: Ting Wang, Changxi Wang, Jinghua Wu, Chenyang He, Wei Zhang, Jiayun Liu, Ruifang Zhang, Yonggang Lv, Yongping Li, Xiaojing Zeng, Hongzhi Cao, Xiuqing Zhang, Xun Xu, Chen Huang, Ling Wang, Xiao Liu
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 5 Issue 2 Pg. 148-156 (02 2017) ISSN: 2326-6074 [Electronic] United States
• PMID: 28039161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Complementarity Determining Regions
• Receptors, Antigen, T-Cell
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Biomarkers, Tumor
• Breast Neoplasms (diagnosis, genetics, immunology)
• Complementarity Determining Regions (genetics)
• Female
• Genetic Variation
• Humans
• Lymph Nodes (immunology, metabolism, pathology)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism, pathology)
• Receptors, Antigen, T-Cell (genetics)
• Receptors, Antigen, T-Cell, alpha-beta (genetics)
• T-Lymphocytes (immunology, metabolism, pathology)