High expression of the checkpoint molecule PD-1 on regulatory and helper CD4+ T cells in metastatic breast cancer patients with poor prognosis

M. Esmail, M. Attia, Sameh Abd-Alaziz, S. El-Naggar, M. Salem
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Abstract

Background: Recurrence and metastasis are common in patients of breast cancer even after chemotherapy and radiotherapy. This recurrence may occur due to the emergence of immunoregulatory T (Treg) cells and the immune checkpoint molecules such as programmed cell death protein 1 (PD-1) which are known to suppress anti-tumor immunity. Aim: The aim of this study is to investigate the numbers of Treg cells and the expression of PD-1 molecule on T cells in the peripheral blood of breast cancer patients at different stages (II, III, and IV) compared to healthy individuals. Materials and Methods: Blood samples were collected from early diagnosed metastatic cancer patients before surgery. Leucocytes were stained with different antibodies including CD4, CD25, CD127, and PD1, and then were analyzed by multiparametric flow cytometry. Results: The results showed that the relative and absolute numbers of Treg cells were significantly increased in breast cancer patients. Interestingly, we found a correlation between the numbers and cancer progression from stages II to III and IV, as compared with healthy individuals. Furthermore, significant increases in PD-1 expression were observed on Treg cells and CD4+ T cells in cancer patients as compared to healthy controls. This profile of PD-1 expression was also correlated with the poor prognosis of the patients. Conclusion: The results provide a better understanding of the immunomodulatory role of Treg cells and PD-1 expression in breast cancer patients who are the target for immunotherapy using checkpoint inhibitors.
在预后不良的转移性乳腺癌患者中调节性和辅助性CD4+ T细胞检查点分子PD-1的高表达
背景:乳腺癌患者在化疗和放疗后复发和转移是常见的。这种复发可能是由于免疫调节性T (Treg)细胞和免疫检查点分子(如程序性细胞死亡蛋白1 (PD-1))的出现而发生的,这些分子已知可抑制抗肿瘤免疫。目的:本研究的目的是研究不同分期(II期、III期、IV期)乳腺癌患者外周血Treg细胞数量及PD-1分子在T细胞上的表达情况。材料与方法:术前采集早期诊断的转移性肿瘤患者的血液样本。用CD4、CD25、CD127、PD1等不同抗体对白细胞进行染色,并用多参数流式细胞术进行分析。结果:乳腺癌患者中Treg细胞的相对数量和绝对数量均明显增加。有趣的是,与健康个体相比,我们发现从II期到III期和IV期的数量与癌症进展之间存在相关性。此外,与健康对照组相比,在癌症患者的Treg细胞和CD4+ T细胞上观察到PD-1表达的显著增加。这种PD-1表达谱也与患者的不良预后相关。结论:该结果为更好地理解Treg细胞和PD-1表达在使用检查点抑制剂进行免疫治疗的乳腺癌患者中的免疫调节作用提供了依据。
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