T lymphocytes infiltrate the microenvironment of breast cancer (BC) tumors and play a pivotal role in tumor immune surveillance. Relationships between the T-cell receptors (TCRs) 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, BC. Our study elucidated the high heterogeneity of the TCR repertoire, and provides potential for future improvements in immune-related diagnosis, therapy, and prognosis for BC patients.
- Received May 18, 2016.
- Revision received November 15, 2016.
- Accepted December 5, 2016.
- Copyright ©2016, American Association for Cancer Research.