吲哚胺-2,3-双加氧酶在非小细胞肺癌中的表达及意义

背景与目的免疫耐受(Tumor tolerance)在肿瘤的发生、发展和转移中发挥了重要作用,但其发生机制尚不完全清楚。本课题拟通过研究吲哚胺2,3-双加氧酶(indoleamine-2,3-dioxygenase,IDO)在非小细胞肺癌(Non-small cell lung cancer,NSCLC)细胞中的表达和调节性T细胞(Regulatory T cell,Treg)在肺癌组织和转移淋巴结内的分布来探讨IDO在诱导肺癌免疫耐受中的机制。方法收集在第三军医大学附属新桥医院和西南医院手术治疗的62例患者肺癌组织和周围正常肺组织、以及15例肺良性病变组织的新鲜标本和石蜡切片。采用免疫组织化学SP法和荧光半定量RT-PCR方法检测IDO蛋白和cDNA在肺癌组织、周边正常肺组织和肺良性病变组织中的表达,并利用免疫组化SP法检测Treg细胞在上述各种组织内的分布情况。结果肺癌组织、周边正常肺组织和肺良性病变组织中IDO表达阳性率分别为67.7%(42/62)、0和13.3%(2/15),前者与后二者比较有统计学差异(P<0.01),转移淋巴结内肺癌细胞IDO表达阳性率为75.0%(15/20),荧光半定量RT- PCR结果与免疫组化基本一致;肺癌组织、转移淋巴结、周边正常肺组织和肺良性病变组织中Treg细胞阳性率分别为83.9%(52/62)、90.0%(18/20)、0和13.3%(2/15),前二者与后二者相互比较有差异(P<0.01),前二者之间或后二者之间相比较差异无统计学意义(P>0.05),IDO阳性表达率与Treg细胞阳性率之间具有相关性(P<0.01)。结论IDO在NSCLC细胞和转移淋巴结内主要为高表达,在周边正常肺组织和肺良性病变中主要为低表达,Treg细胞在NSCLC组织和转移淋巴结内主要为阳性,而在正常肺组织和肺良性病变中主要为阴性,提示肺癌组织和转移性淋巴结内的免疫耐受可能与NSCLC细胞通过增强IDO表达来促进Treg细胞增殖有关。

The expression and significance of indoleamine-2,3-dioxygenase in non-small cell lung cancer cell

Background and Objective Immune tolerance plays the key role in the initiation,develop- ment and metastasis of the malignant disease.However,the underlging mechanisms have not been completely eluci- dated.The aim of this study is to investigate the expression of indoleamine-2,3-dioxygenase(IDO) in non-small cell lung cancer(NSCLC) and the distribution of regulatory T cell(Treg) in NSCLC tissue and the metastastic lymph node, and the possible relationships between them.Methods This study involved 62 NSCLC patients and 15 control pa- tients with benign diseases that operated in the affiliated Xinqiao hospital and Southwest hospital of the Third Mili- tary Medical University.The expression of IDO in lung cancer cell,the corresponding normal lung tissues and the benign control tissues were detected by SP immunohistochemistry(IHC) and Fluorescent semi-quantitative RT-PCR. The distribution of Treg cell was detected by SP IHC too.The difference of positive rates of IDO was evaluated by Chi-square test and Fisher's exact test.Results The positive expression rates of IDO in lung cancer cells corre- sponding normal lung tissues and bengin disease tissues were 67.7%(42/62),0 and 13.3%(2/15),respectively. There were significant differences between the former and the latter two(P<0.01).The positive expression rate of I- DO in metastastic lymph node was 75.0%(15/20).The results of Fluorescent semi-quantitative RT-PCR were consis- tent with the IHC.The positive rates of Treg cells in lung cancer tissues,metastastie lymph nodes,corresponding normal lung tissues and bengin disease tissues were 83.9%(52/62),90.0%(18/20),0 and 13.3%(2/15),respectively. Significant difference was also found between the former two and the latter two(P<0.01),but there was no signifi- cant differences between the two formers or the two latters(P>0.05).There was significant difference between the positive rate of IDO expression and the distribution of Treg cell(P<0.01).Conclusion IDO expression is up-reg- ulated in NSCLC cell and metastastic lymph nodes.Treg cell is positive in lung cancer tissues and metastastic lymph node.These results have importment implication that the IDO( ) cancer cell might be concerned with the tumor im- mune tolerance by inducing the proliferation of Treg cells.