吲哚胺2,3-双加氧酶参与乳腺癌患者免疫耐受的研究

摘要

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) and to explore 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,benign diseases and normal breast tissues.Immunohistochemistry was used to detect the expression of IDO and Foxp3 proteins in the same tissues. Results:The mRNA and the percentage of IDO~+ cells [(19.59±7.65)%] in TDLNs were higher than in breast cancer [(13.16±7.82)%] (P<0.05),while in the breast cancer were higher than in benign diseases [(3.24±1.30)%] and normal breast tissue [(2.70±1.53)%] (P<0.05).Expression of IDO protein in breast cancer was associated with tumor clinical stage and lymph nodes metastasis while had no relationship with tumor diameter,ER,PR and Her2 status.The percentage of Foxp3~+ cells in breast cancer [(3.50±1.04)%] was higher than in benign diseases [(0.71±0.42)%] (P<0.05) and normal breast tissue [(0.55±0.34)%],and that of the TDLNs [(6.13±2.31)%] was higher than in breast cancer [(3.50±1.04)%] (P<0.05).The percentage of IDO~+ cells was positive correlated with the distribution of Treg cells in breast cancer(r~2=0.449,P<0.05)and TDLNs (r~2=0.454,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.%目的:研究吲哚胺2,3-双加氧酶(Indoleamine2,3-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、癌旁正常乳腺、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(13.16±7.82)%](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(3.24±1.30)%]和癌旁正常乳腺组织[IDO阳性细胞指数(2.70±1.53)%](P均<0.05).乳腺癌组织中IDO表达水平与肿瘤临床分期和淋巴结转移相关(P<0.05).乳腺癌引流淋巴结中Foxp3阳性细胞指数[(6.13±2.31)%]高于乳腺原发癌[(3.50±1.04)%],乳腺癌组织中Foxp3阳性细胞指数高于乳腺良性病变[(0.71±0.42)%]和癌旁正常乳腺组织[(0.55±0.34)%](P均<0.05).乳腺癌和引流淋巴结中IDO的表达水平与Treg细胞的分布间均正性相关(r~2=0.449,r~2=0.454,P均<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.