中国免疫学杂志,2009(25)11,987-990转995
吲哚胺2,3-双加氧酶参与乳腺癌患者免疫耐受的研究
中国图书分类号 R392 文献标识码 A 文章编号1000-484x(2009)11-0987-05
[摘要] 目的:研究吲哚胺2,3-双加氧酶(indoleamine-2 3-dioxygenase, IDO)在乳腺癌组织和引流淋巴结中的表达及调节性T细胞在相应组织内的分布,探讨IDO在乳腺癌免疫耐受中的作用机制。方法 收集26例乳腺癌患者的癌组织、癌旁、引流淋巴结和10例乳腺良性病变组织,用RT-PCR法检测IDO mRNA表达,用免疫组织化学法检测IDO和Foxp3蛋白表达。结果 乳腺癌引流淋巴结中IDO mRNA表达水平及IDO表达阳性指数[(19.59±7.65)%]高于原发乳腺癌组织[IDO表达阳性指数(13.60±7.89)%](P<0.05),乳腺癌组织中IDO mRNA表达水平及IDO表达阳性指数高于乳腺良性病变组织[IDO表达阳性指数(3.25±1.29)%]和癌旁正常乳腺组织[IDO表达阳性细胞指数(2.70±1.53)%](P均<0.05)。乳腺癌组织中IDO表达水平与病理类型和临床分期相关(P<0.05)。乳腺癌引流淋巴结中Treg细胞阳性指数(2.68%)高于乳腺原发癌(2.67±1.18%),乳腺癌组织中Treg细胞阳性指数高于乳腺良性病变(0.45±0.21%)和癌旁正常乳腺组织(0.55±0.34%)(P均<0.05)。乳腺癌组织中IDO阳性表达指数与Treg细胞的阳性指数呈正性相关(r2=0.449, P<0.05),与引流淋巴结中Treg细胞阳性指数呈正性相关(r2=0.515,P<0.05)。结论:IDO在乳腺癌细胞中表达增高,并伴随乳腺癌和引流淋巴结中Treg细胞比例升高,提示IDO表达增高有可能通过募集Treg细胞参与肿瘤和引流淋巴结内的免疫耐受。
[关键词] 乳腺癌;吲哚胺2,3-双加氧酶;免疫耐受;Treg细胞
The mechanism of indoleamine-2,3-dioxygenase participating breast cancer immune tolerance
[Abstract] Objective:To investigate the expression of indoleamine-2, 3-dioxygenase and the distribution of Treg cells in breast cancer and
tumor draining lymph nodes(TDLNs),then to seek the relationship between them. Methods:26 cases of breast cancer and 10 cases of breast benign diseases were collected from Tianjin medical university cancer hospital. RT-PCR was used to detect the mRNA of IDO in breast cancer, TDLNs and benign diseases;Immunohistochemistry was used to detect the expression of IDO and Foxp3 proteins in the same tissue. Results:The mRNA and the positive ratio[(19.59±7.65)%] of IDO in TDLNs were higher than breast cancer[(13.60±7.89)%] (P<0.05).The breast cancer were higher than benign diseases[(3.25±1.29)% ] and normal breast tissue[(2.70±1.53)%] (P<0.05). Expression of IDO protein in breast cancer was associated with clinical stage and pathological type while had no relationship with tumor diameter, lymph nodes metastasis, ER, PR and Her2 status. The positive ratio of Treg cells in breast cancer[(2.67±1.59)%]was higher than the benign diseases[(0.45±0.21)%](P<0.05) and normal breast tissue (0.55±0.34%),while the TDLNs[(5.92±2.68)%] was higher than breast cancer[(2.67±1.59)%] (P<0.05). Expression of IDO was positive correlation with the distribution of Treg cells in breast cancer(r2=0.449, P<0.05)and in TDLNs(r2=0.515, P<0.05). Conclusion:Expression of IDO in breast cancer is upregulated. The high level expression of IDO is accompanied by increasing Treg cells in breast cancer and TDLNs,which suggests that breast cancer can recruit Treg cells by expressing IDO to participate the immune tolerance.
[Key words] breast cancer;indoleamine-2,3-dioxygenase;immune tolerance;Treg cells