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.

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

“…The TCR repertoire overlap was always used to evaluate the similarity of TCR repertoires between samples, calculated as the total number of shared productive aa sequences divided by the sum of productive aa sequences detected in 2 samples 24. We quantified the similarity of TCR repertoire between tumor and adjacent normal tissues by overlap, and investigated it's relation with the TNM stage or prognosis.…”

“…Firstly, we performed the TCR sequencing using increased sequencing reads and read length, which could contribute to obtaining a more reliable data and conclusion. Secondly, we used the U/T index and the Clonality index rather than the number of productive unique aa sequences or Shannon diversity index to assess the diversity of TCR repertoire, as the former 2 indexes could better correct the impact of uneven reads amount 13, 22, 24. Using the different sequencing depth or the different diversity indicators might be another reason for the inconsistent results.…”

Computational approaches for characterizing the tumor immune microenvironment

“…Immune repertoire sequencing has enabled researchers to study immune cell heterogeneity in different tumor types, which has important implications in prognosis and therapy development . TCR sequencing has also been used to understand repertoire diversity in T‐cell response to immune checkpoint blockade therapy.…”

Mice developing mammary tumors evolve T cell sequences shared with human breast cancer patients

“…To learn whether our observations in the mouse model might be relevant to human breast cancer, we compared the mouse TCR data to three, previously published human TCR datasets, each of which focused on a different aspect of breast cancer (Figure 3a) (Beausang et al, 2017;Page et al, 2016;Wang et al, 2017): Beausang et al (Beausang et al, 2017) studied T cell receptors in early-stage breast cancer and sampled the tumor tissue, the surrounding normal tissue and peripheral blood. Wang et al (Wang et al, 2017) sequenced the TCR repertoires of breast cancer tumors, lymph nodes and adjacent tissue. Page et al (Page et al, 2016) studied breast cancer after immunotherapy.…”