胃癌组织吲哚胺2，3-双加氧酶表达及其诱导肿瘤免疫逃逸的研究

Expression and clinical significance of indoleamine 2,3-dioxygenase-mediated immune escape in gastric cancer

目的:检测胃癌组织中吲哚胺2,3双加氧酶(indoleamine2,3-dioxygenase,IDO)、增殖细胞核抗原(PCNA)、T细胞表面标志CD3、CD4和CD25的表达状况,探讨其在肿瘤细胞增殖、转移和免疫逃逸中的作用。方法:采用免疫组化染色及免疫荧光染色检测胃癌组织中IDO、PCNA、T细胞表面标志CD3、CD4和CD25的表达,分析IDO表达在肿瘤细胞增殖、转移和免疫逃逸中的作用。结果:1)肿瘤细胞和单个核细胞表面表达IDO;胃癌肿瘤组织IDO的阳性表达率为73.33%,高于癌旁组织。肿瘤组织内IDO高表达与PCNA高表达显著相关,χ2=4.35,P<0.05。2)胃癌肿瘤组织内CD3阳性表达率为37.67%,低于癌旁对照组,χ2=4.45,P<0.05。3)胃癌组织中可见CD4+CD25+调节性T细胞(Treg)。4)胃癌患者中转移组IDO阳性表达率为86.36%,无转移组表达率为60.0%,转移组IDO阳性表达率高于无转移组,P=0.01。结论:胃癌细胞高表达IDO,能抑制T细胞活化、增殖和向肿瘤组织内的浸润,在肿瘤组织内造成免疫抑制,从而促进肿瘤的增殖和转移。肿瘤组织中CD4+CD25+Treg细胞参与IDO引发胃癌肿瘤免疫耐受的过程,发挥免疫抑制作用。

OBJECTIVE： To investigate the expression of IDO （indoleamine 2,3-dioxygenase） in gastric cancer, as well as its clinical significance. METHODS：Expressions of IDO, PCNA, CD3, CD4 and CD25 were detected by immunochemistry and immunofluorescence technique in gastric cancer. RESULTS： 1）The positive rate of IDO expression in GC cases （73.33%） was higher than that in Para cases （61.90%）. IDO was detected in membrane on cancer cells and mononuclear cells. Moreover, the over expression of IDO in cancer tissue was relative with over expression of PCNA,Х^2 =4.35,P〈0.05. 2） The positive rates of CD3 expression in GC cases and Para cases were 37.67% and 66.67% respectively. There was a significant difference between the two groups, Х^2=4.45, P〈0.05. 3）CD4^＋CD25^＋ T cells were exanimated in gastric cancer. 4）The positive rates of IDO expression was 86.36% with lymph node metastasis of 30 cases gastric cancer, and 60.0% without lymph node metastasis （P = 0.01 ）. CONCLUSIONS： Strong expression of IDO in gastric cancer can inhibit activation, proliferation and infiltration of T cells, which results in the environment of immunosuppression in cancer tissue and encourage proliferation and metastasis of cancer cells. CD4^＋ CD25^＋ T cells in cancer is related to the expression of IDO, which indicates Treg participates immune tolerance induced by IDO.