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乳腺癌新辅助化疗中调节性 T 细胞与外周血 T 淋巴细胞亚群的临床意义

英文原题:Clinical significance of regulatory T cells and T lymphocyte subsets in peripheral blood in neoadjuvant chemotherapy for breast cancer.

PubMed 2023/07/15(内容时间) Am J Cancer Res Q2 · IF 3.1(JCR 2025)

研究概要

与对照组相比,乳腺癌患者CD3+、CD4+、CD4+/CD8+比值及NK细胞显著降低(P < 0.05),而Treg和CD8+细胞水平显著升高(P < 0.05)。

中文摘要

免疫反应对乳腺癌新辅助化疗疗效的影响在很大程度上仍不清楚。为表征调节性 T 细胞(CD4 + CD25 + CD127 low Treg)、T 淋巴细胞亚群(CD3 +、CD4 +、CD4 + /CD8 +)和 NK 细胞在新辅助化疗中的作用,我们研究了这些免疫细胞亚群与乳腺癌进展的相关模式。回顾性收集 2019 年 5 月至 2021 年 11 月在南京市妇幼保健院接受新辅助化疗的 120 例乳腺癌患者作为乳腺癌组,并选取 46 例健康女性作为对照组。通过流式细胞术分析外周血中调节性 T 细胞、T 淋巴细胞亚群和 NK 细胞的数量。与对照组相比,乳腺癌患者中 CD3 +、CD4 +、CD4 + /CD8 + 比值和 NK 细胞显著降低(P < 0.05),而 Treg 和 CD8 + 细胞水平显著升高(P < 0.05)。此外,不同临床分期乳腺癌患者的免疫反应状态明显不同。在较高的肿瘤分期中,CD3 +、CD4 +、CD4 + /CD8 + 比值和 NK 细胞水平降低,而 Treg 和 CD8 + T 细胞水平逐渐升高。此外,我们发现 CD3 +、CD4 +、CD4 + /CD8 + 和 NK 细胞百分比较低与淋巴结转移相关,同时伴有较高数量的 CD8 + T 细胞。有趣的是,新辅助化疗治疗后,患者的Tregs、CD3+、CD4+水平及CD4+/CD8+比值均较治疗前上调,表明细胞毒性淋巴细胞恢复,同时免疫抑制微环境得到巩固(P < 0.05)。免疫功能障碍在乳腺癌患者中常见,与肿瘤进展和淋巴结转移密切相关。研究发现,新辅助化疗高度影响T淋巴细胞数量,并改善乳腺癌患者T淋巴细胞亚群的免疫功能。同时,作为免疫抑制细胞,Tregs(CD4+CD25+CD127 low Treg)的比例在新辅助化疗治疗后也增加。我们的结果为在新辅助化疗期间开发新的联合策略以逆转免疫抑制微环境并实现更好的临床结局提供了指导。

展开英文摘要原文

The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4 + CD25 + CD127 low Treg), T lymphocyte subsets (CD3 + , CD4 + , CD4 + /CD8 + ) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3 + , CD4 + , CD4 + /CD8 + ratio and NK cells were significantly decreased in patients with breast cancer ( P < 0.05), while the levels of Treg and CD8 + cells were significantly increased ( P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3 + , CD4 + , CD4 + /CD8 + ratio and NK cell were reduced, while the level of Treg and CD8 + T cells gradually increased. Furthermore, we found a lower percentage of CD3 + , CD4 + , CD4 + /CD8 + and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8 + T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3 + , CD4 + and CD4 + /CD8 + ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time ( P < 0.05 ). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4 + CD25 + CD127 low Treg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.

论文信息

作者
Mao XD、Chen SZ、Shen SQ、Liu KS
第一作者单位
Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210028, Jiangsu, China.China
通讯作者单位
Department of Clinical Laboratory, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital Nanjing 210029, Jiangsu, China.China
期刊
American journal of cancer research2023
原文标识
PubMed 37559980