Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
BGI-Shenzhen, Shenzhen, China.
Cancer Immunol Res. 2017 Feb;5(2):148-156. doi: 10.1158/2326-6066.CIR-16-0107. Epub 2016 Dec 30.
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.
T 淋巴细胞浸润乳腺癌肿瘤的微环境,并在肿瘤免疫监测中发挥关键作用。在人类乳腺癌中,肿瘤内、周围组织和引流淋巴结中 T 细胞所携带的 T 细胞受体(TCR)之间的关系在很大程度上尚未得到探索。因此,关于这些组织之间可能的 T 细胞交换的相对程度的信息也缺乏。在这里,我们使用多重 PCR 分析了肿瘤、相邻非肿瘤和乳腺癌患者腋窝淋巴结组织中 T 细胞的 TCR 库,并对 TCRβ 链进行了高通量测序。肿瘤中 T 细胞库的多样性低于淋巴结,但高于非肿瘤组织,并且优先使用可变和连接基因。这些数据与以下假设一致,即肿瘤中的大多数 T 细胞来自淋巴结,然后在肿瘤组织中扩增。阳性淋巴结似乎增强了 T 细胞向肿瘤的浸润以及淋巴结中 T 细胞的克隆扩增。此外,在腔细胞样乳腺癌中,肿瘤和非肿瘤组织之间的 TCR 库相似性明显高于基底样乳腺癌。我们的研究阐明了 TCR 库的高度异质性,并为未来改善乳腺癌患者的免疫相关诊断、治疗和预后提供了潜力。Cancer Immunol Res; 5(2); 148-56. ©2016 AACR.