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.
Highlights
Tumorigenesis is regulated by immune responses to neoantigens in the tumor microenvironment, including the plasticity of macrophage [1] and suppression of antitumor immune response [2, 3]
IHC staining and careful scoring of the T lymphocytes in the tissues revealed that the proportion of infiltrated T lymphocytes into the tumor microenvironment varied considerably among tumors and adjacent nontumor tissues (Table 1)
Using IHC and TRB CDR3 deep sequencing, we unraveled an unpredicted degree of heterogeneity of T lymphocyte in tumor and other tissues in breast cancer patients
Summary
Tumorigenesis is regulated by immune responses to neoantigens in the tumor microenvironment, including the plasticity of macrophage [1] and suppression of antitumor immune response [2, 3]. More than a decade ago, Schreiber proposed the three "E roles" (elimination, equilibrium, and escape) of immune surveillance, which interprets the interaction between tumor and host immune system in tumor progression [4]. Lymphocytes are the major antitumor cells in tumor microenvironments, and many studies have demonstrated that tumor-infiltrating lymphocytes (TILs), especially CD8þ T cells, are related to improved clinical prognosis in most of the tumor types [5], such as ovarian cancer [6], cervical cancer [7], Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
