Mao Xiao-Dong, Chen Su-Zhu, Shen Su-Qing, Liu Kang-Sheng
Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210028, Jiangsu, China.
Key Laboratory of TCM Syndrome & Treatment of Yingbing of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine Nanjing 210028, Jiangsu, China.
Am J Cancer Res. 2023 Jul 15;13(7):3091-3099. eCollection 2023.
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 (CD4CD25CD127Treg), 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 ( < 0.05), while the levels of Treg and CD8 cells were significantly increased ( < 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 (). 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 (CD4CD25CD127Treg) 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.
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。为了明确调节性T细胞(CD4⁺CD25⁺CD127⁻Treg)、T淋巴细胞亚群(CD3、CD4、CD4/CD8)和自然杀伤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。回顾性收集了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。采用流式细胞术分析外周血中调节性T细胞、T淋巴细胞亚群和自然杀伤细胞的数量。与对照组相比,乳腺癌患者的CD3、CD4、CD4/CD8比值和自然杀伤细胞显著降低(P<0.05),而调节性T细胞和CD8细胞水平显著升高(P<0.05)。此外,不同临床分期的乳腺癌患者免疫反应状态明显不同。在较高肿瘤分期中,CD3、CD4、CD4/CD8比值和自然杀伤细胞水平降低,而调节性T细胞和CD8⁺T细胞水平逐渐升高。此外,我们发现CD3、CD4、CD4/CD8和自然杀伤细胞百分比降低与淋巴结转移相关,同时CD8⁺T细胞数量增多。有趣的是,新辅助化疗治疗后,患者的调节性T细胞、CD3、CD4和CD4/CD8比值水平均较治疗前上调,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普遍存在,这与肿瘤进展和淋巴结转移密切相关。发现新辅助化疗对乳腺癌患者T淋巴细胞数量有高度影响,并改善T淋巴细胞亚群的免疫功能。同时,作为免疫抑制细胞,新辅助化疗治疗后调节性T细胞(CD4⁺CD25⁺CD127⁻Treg)比例也增加。我们的结果为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果提供了指导。