Analysis of the Heterogeneity of CD4+CD25+ T Cell TCR β CDR3 Repertoires in Breast Tumor Tissues, Lung Metastatic Tissues, and Spleens from 4T1 Tumor-Bearing BALB/c Mice.

Teng Zhang,Danhua Su,Xiaoyan He,Long Ma,Xinsheng Yao,Bin Shi,Suhong Sun,Rui Ma,Jiezuan Yang,Fangfang Duan

doi:10.1155/2020/3184190

Teng Zhang, Danhua Su + Show 8 more

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https://doi.org/10.1155/2020/3184190

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Abstract

To study the homogeneity and heterogeneity of CD4+CD25+ T cells receptor β-chain complementarity determining region 3 (TCR β CDR3) repertoires in breast tumor tissues, lung metastatic tissues, and spleens from 4T1 tumor-bearing BALB/c mice. We used high-throughput sequencing to analyze the characteristics and changes of CD4+CD25+ TCR β CDR3 repertoires among tumor tissues, lung metastatic tissues, and spleens. The diversity of the CD4+CD25+ TCR β CDR3 repertoires in breast tumor tissue was similar to that of lung metastatic tissues and less pronounced than that of spleen tissues. Breast tumor tissues and lung metastatic tissues had a greater number of high-frequency CDR3 sequences and intermediate-frequency CDR3 sequences than those of spleens. The proportion of unique productive CDR3 sequences in breast tumor tissues and lung metastatic tissues was significantly greater than that in the spleens. The diversity and frequency of the CDR3 repertoires remained homogeneous in breast tumors and lung metastatic tissues and showed great heterogeneity in the spleens, which suggested that the breast tissues and lung metastatic tissues have characteristics of CD4+CD25+ T cells that relate to the tumor microenvironment. However, the number and characteristics of overlapping CDR3 sequences suggested that there were some different CD4+CD25+ T cells in tumors and in the circulatory immune system. The study may be used to further explore the characteristics of the CDR3 repertoires and determine the source of the CD4+CD25+ T cells in the breast cancer microenvironment.

Highlights

Given the link between inflammation and cancer, and the presence of immune cells in the tumor microenvironment, it is very important to study the antitumor immune response and tumor immune escape
CD4+CD25+ T cells of FCM detection were all above 84% (Figure 2); the DNA concentration and purity of CD4+CD25+ T cells were shown in Figure S1, Supplement Table 1, and Supplement Tables 2
The number of CD4+CD25+Tregs in patients with breast cancer was found to decrease after chemotherapy or radiotherapy

Summary

Introduction

Given the link between inflammation and cancer, and the presence of immune cells in the tumor microenvironment, it is very important to study the antitumor immune response and tumor immune escape. CD4+CD25+T cells is a subset of T cells, which plays an important role in the body inflammation and immune response [1, 2]. Research has showed that the absolute number or subset of CD4+CD25+Tregs increases in peripheral blood, lymph node, and tumor tissue of patients with breast cancer and closely related to the pathological type of breast cancer and progress [4,5,6,7,8,9]. The number of Tregs in peripheral blood of breast cancer patients with stages III and IV is significantly higher than stages I and II, and cancer tissues are higher than that of adjacent tissues [10].

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