Journal
CANCER IMMUNOLOGY RESEARCH
Volume 5, Issue 2, Pages 148-156Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-16-0107
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Funding
- National Natural Science Fund [81272899, 81672593, 30973463, 81470120]
- Shaanxi Fund [2013K12-03-03, 2014JM4087]
- Xi'an Fund [SF1323(3)]
- Discipline Booster Plan of the Xijing Hospital [2014JM4087, XJZT12Z07]
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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 TCR beta 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. (C) 2016 AACR.
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