化疗对乳腺癌患者外周血中Treg细胞的影响及意义
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摘要
目的Treg(CD_4~+CD_(25)~+调节性T细胞)可以抑制T细胞以及NK细胞的增殖和活化,在维持免疫系统稳定、防止自身免疫性疾病方面具有重要作用;但近几年的研究表明Treg细胞在肿瘤免疫抑制方面同样扮演了重要的角色。本研究旨在研究化疗药物对乳腺癌患者根治术后外周血中Treg细胞的影响及意义,为乳腺癌综合治疗提供有益的资料。
方法采集52例乳腺癌术后患者化疗前1天及化疗后第10天外周静脉血,52例乳腺癌患者均给予TE方案(多西紫杉醇+表阿霉素)化疗,患者病理类型经术后病理组织学诊断均为浸润性导管癌。应用流式细胞技术检测外周血中Treg细胞以及CD_3~+、CD_4~+、CD_8~+T细胞占T淋巴细胞百分比,采用ELLSA法检测外周血中IL-4、IL-10、TGF-β1和IFN-γ的表达水平。
结果
1化疗后乳腺癌患者外周血中Treg细胞占T淋巴细胞百分比(4.75±1.60)%较化疗前(5.59±1.81)%减少(P＜0.05),且Treg细胞变化与患者年龄、淋巴结有无转移、淋巴结转移数量以及绝经状态无关(P＞0.05)。
2化疗前后CD_3~+细胞占T淋巴细胞比例分别为(64.690±7.469)%,(64.357±9.356)%,(P＞0.05)。化疗前后CD_4~+T细胞占T淋巴细胞比例分别为(38.048±10.671)%,(36.536±9.664)%,(P＞0.05)。
3化疗后CD_8~+T细胞占T淋巴细胞比例(28.129±10.900)%较化疗前(24.876±6.631)%升高(P＜0.05)。化疗后CD_4~+/CD_8~+(1.506±0.691)较化疗前(1.680±0.704)降低(P＜0.05)。
4化疗前后Treg细胞比例变化与CD_3~+T细胞变化以及CD_4~+/CD_8~+变化无相关性(P＞0.05)。
5化疗后乳腺癌患者外周血中IL-4、IL-10、TGF-β1浓度较化疗前降低,而IFN-γ浓度增高(P均＜0.05)。
6化疗前后Treg细胞比例变化与细胞因子IL-4、IL-10、TGF-β1和IFN-γ浓度变化无明显相关(P＞0.05)。
结论化疗可使乳腺癌患者外周血中Treg细胞占T淋巴细胞比例降低,CD_8~+T淋巴细胞亚群比例增加,有助于提高肿瘤治疗的效果。化疗后乳腺癌患者外周血中可溶性细胞因子IL-4、IL-10、TGF-β1和IFN-γ浓度发生变化,但尚不能证明Treg细胞通过以上细胞因子在肿瘤免疫中发挥抑制作用。
Objective T cells constitutively expressing CD4 and CD 25 marker are essential for maintenance of self-tolerance and have been referred to as regulatory T cells(Treg).Treg also have been reported to be potent inhibitors of an antitumor immune response.The current study was designed to investigate the effect of chemotherapy on Treg in peripheral blood of patients with breast cancer who received radical mastectomy or modify radical mastectomy, providing some dates for chemoimmunotherapy of breast cancer.
Methods 52 peripheral blood of post-operated patients with breast cancer were collected 1 day before chemotherapy and the 10th day after chemotherapy, who were all diagnosed with infiltrating ductal carcinoma finally and administrated with docetaxel and pharmorubicin.The proportion of Treg and CD_3~+、CD_4~+、CD_8~+T cells in the total amount T cells was evaluated by flow cytometry analysis.The cytokine suchas IL-4、IL-10、TGF-β1 and IFN-γwere measured by the ELLSA method.
Results
1 The proportion of Treg in peripheral.blood from post-chemo patients with breast cancer is less than the pre-chemo patients,(4.75±1.60)%versus (5.59±1.81)%(P＜0.05),and the change of Treg is not correlate with age, lymph node +/－,the number of positive lymph node and menopaused status(P＞0.05).
2 The percentage of CD_3~+、CD_4~+ T cells in peripheral blood of patients with breast cancer are not significantly different after chemotherapy, (64.690±7.469)%versus(64.357±9.356)%(P＞0.05),(38.048±10.671)% versus(36.536±9.664)%(P＞0.05).
3 The prevalence of CD_8~+ T cells in T lymphocytes increased from (24.876±6.631)%to(28.129±10.900)%after chemotherapy(P＜0.05), but while CD_4~+/CD_8~+ decreased from(1.680±0.704)%to(1.506±0.691)% (P＜0.05).
4 The change of CD_8~+ T cells and CD_4~+/CD_8~+ were not correlate with the change of Treg after chemotherapy.
5 The levels of IL-4、IL-10 and TGF-β1 are lower after chemotherapy than those before chemotherapy(P＜0.05),while the level of IFN-γis higher(P＜0.05).
6 The change of Treg is not correlate with the change of cytokines such as IL-4、IL-10、TGF-β1 and IFN-γ.
Conclusion Chemotherapy may enhance anti-tumor efficiency through reducing Treg in peripheral blood of patients with breast cancer.The levels of cytokine such as IL-4、IL-10、TGF-β1 and IFN-γare changed after chemotherapy,but the antitumor immunosuppressive features of Treg is not significant correlated with these cytokines.
方法采集52例乳腺癌术后患者化疗前1天及化疗后第10天外周静脉血,52例乳腺癌患者均给予TE方案(多西紫杉醇+表阿霉素)化疗,患者病理类型经术后病理组织学诊断均为浸润性导管癌。应用流式细胞技术检测外周血中Treg细胞以及CD_3~+、CD_4~+、CD_8~+T细胞占T淋巴细胞百分比,采用ELLSA法检测外周血中IL-4、IL-10、TGF-β1和IFN-γ的表达水平。
结果
1化疗后乳腺癌患者外周血中Treg细胞占T淋巴细胞百分比(4.75±1.60)%较化疗前(5.59±1.81)%减少(P＜0.05),且Treg细胞变化与患者年龄、淋巴结有无转移、淋巴结转移数量以及绝经状态无关(P＞0.05)。
2化疗前后CD_3~+细胞占T淋巴细胞比例分别为(64.690±7.469)%,(64.357±9.356)%,(P＞0.05)。化疗前后CD_4~+T细胞占T淋巴细胞比例分别为(38.048±10.671)%,(36.536±9.664)%,(P＞0.05)。
3化疗后CD_8~+T细胞占T淋巴细胞比例(28.129±10.900)%较化疗前(24.876±6.631)%升高(P＜0.05)。化疗后CD_4~+/CD_8~+(1.506±0.691)较化疗前(1.680±0.704)降低(P＜0.05)。
4化疗前后Treg细胞比例变化与CD_3~+T细胞变化以及CD_4~+/CD_8~+变化无相关性(P＞0.05)。
5化疗后乳腺癌患者外周血中IL-4、IL-10、TGF-β1浓度较化疗前降低,而IFN-γ浓度增高(P均＜0.05)。
6化疗前后Treg细胞比例变化与细胞因子IL-4、IL-10、TGF-β1和IFN-γ浓度变化无明显相关(P＞0.05)。
结论化疗可使乳腺癌患者外周血中Treg细胞占T淋巴细胞比例降低,CD_8~+T淋巴细胞亚群比例增加,有助于提高肿瘤治疗的效果。化疗后乳腺癌患者外周血中可溶性细胞因子IL-4、IL-10、TGF-β1和IFN-γ浓度发生变化,但尚不能证明Treg细胞通过以上细胞因子在肿瘤免疫中发挥抑制作用。
Objective T cells constitutively expressing CD4 and CD 25 marker are essential for maintenance of self-tolerance and have been referred to as regulatory T cells(Treg).Treg also have been reported to be potent inhibitors of an antitumor immune response.The current study was designed to investigate the effect of chemotherapy on Treg in peripheral blood of patients with breast cancer who received radical mastectomy or modify radical mastectomy, providing some dates for chemoimmunotherapy of breast cancer.
Methods 52 peripheral blood of post-operated patients with breast cancer were collected 1 day before chemotherapy and the 10th day after chemotherapy, who were all diagnosed with infiltrating ductal carcinoma finally and administrated with docetaxel and pharmorubicin.The proportion of Treg and CD_3~+、CD_4~+、CD_8~+T cells in the total amount T cells was evaluated by flow cytometry analysis.The cytokine suchas IL-4、IL-10、TGF-β1 and IFN-γwere measured by the ELLSA method.
Results
1 The proportion of Treg in peripheral.blood from post-chemo patients with breast cancer is less than the pre-chemo patients,(4.75±1.60)%versus (5.59±1.81)%(P＜0.05),and the change of Treg is not correlate with age, lymph node +/－,the number of positive lymph node and menopaused status(P＞0.05).
2 The percentage of CD_3~+、CD_4~+ T cells in peripheral blood of patients with breast cancer are not significantly different after chemotherapy, (64.690±7.469)%versus(64.357±9.356)%(P＞0.05),(38.048±10.671)% versus(36.536±9.664)%(P＞0.05).
3 The prevalence of CD_8~+ T cells in T lymphocytes increased from (24.876±6.631)%to(28.129±10.900)%after chemotherapy(P＜0.05), but while CD_4~+/CD_8~+ decreased from(1.680±0.704)%to(1.506±0.691)% (P＜0.05).
4 The change of CD_8~+ T cells and CD_4~+/CD_8~+ were not correlate with the change of Treg after chemotherapy.
5 The levels of IL-4、IL-10 and TGF-β1 are lower after chemotherapy than those before chemotherapy(P＜0.05),while the level of IFN-γis higher(P＜0.05).
6 The change of Treg is not correlate with the change of cytokines such as IL-4、IL-10、TGF-β1 and IFN-γ.
Conclusion Chemotherapy may enhance anti-tumor efficiency through reducing Treg in peripheral blood of patients with breast cancer.The levels of cytokine such as IL-4、IL-10、TGF-β1 and IFN-γare changed after chemotherapy,but the antitumor immunosuppressive features of Treg is not significant correlated with these cytokines.
引文
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