吲哚胺2，3双加氧酶和叉状头转录因子3对胆囊癌免疫耐受的作用及影响  

Indoleamine 2,3-dioxygenase and forkhead boxP3 on immune tolerance of gallbladder carcinoma cells

作　　者：高剑[1] 焦兴元[1] 张鹏[1] 杜军[2] 石景森[3] 

机构地区：[1]广州医学院第二附属医院肝胆外科,510260 [2]广州中山大学药学院微生物与生化制药教研室 [3]西安交通大学医学院第一附属医院普外科

出　　处：《中华肝胆外科杂志》2012年第4期252-255,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：基金项目：本课题受国家自然科学基金资助（30840096）

摘　　要：目的研究吲哚胺2，3双加氧酶（IDO）、叉状头转录因子3（FOXP3）在原发性胆囊腺癌中的表达情况，探讨其对胆囊癌细胞免疫耐受的作用及影响。方法采用免疫组化SP法检测51例原发性胆囊腺癌组织、90例慢性胆囊炎组织和20例正常胆囊组织中ID0和FOXP3的表达情况。结果ID0和FOXP3在胆囊癌组织的阳性率分别为72．5oA（37／51）和60．8％（31／51）；在正常对照组胆囊黏膜阳性表达率分别为5．0％（1／20）和20．0％（4／20）；在胆囊炎及胆囊结石分别为11．1％（10／90）和32．2％（29／90）。三组间ID0和FOXP3阳性表达率差异均有统计学意义（P〈0．01）。ID0在单纯增生、不典型增生、胆囊癌Ⅰ～Ⅲ期和胆囊癌Ⅳ～Ⅴ期的阳性表达率分别为7．1％、17．7％、40．0％和77．4％，FOXP3的阳性表达率分别为14．3％、35．3％、35％和64．5％，ID0和FOXP3在单纯增生、不典型增生、胆囊癌Ⅰ～Ⅲ期和胆囊癌Ⅳ～Ⅴ期的阳性率差异均有统计学意义（IDO：χ^2=50．75，P〈0．01；FOXP3：χ^2=22．79，P〈0．01）。胆囊癌在Nevin不同分期、有无淋巴结或远处转移、有无并发结石组间的ID0和FOXP3的阳性率表达差异均有统计学意义（P值均〈0．05），而不同性别、年龄、组织学分化程度间IDO和FOXP3的阳性率表达差异均无统计学意义（P均〉0．05）。胆囊癌组织中IDO阳性表达率（69．8％）与FOXP3阳性表达率（58．1％）显著正相关（r=0．406，P=0．003）。结论原发性胆囊癌组织中IDO的高表达，以及间质淋巴细胞FOXP3的表达与胆囊癌的免疫耐受密切相关。IDO可能为胆囊癌免疫治疗的新靶点。Objective To investigate the expressions of indoleamine 2,3-dioxygenase （IDO） and transcription factor forkhead box P3 （FOXP3）in gallbladder adenocarcinoma; and to evaluate the relationship between the expressions of IDO and FOXP3 protein, and clinicopathology and lymph node metastasis of gallbladder carcinoma. Methods The expressions of IDO and FOXP3 in 51 cases of primary gallbladder cancer, 90 cases of chronic cholecystitis, and 20 cases of normal gallbladder tissues were studied by immunohistochemical staining. Results The positive expression rates of IDO and FOXP3 in gallbladder carcinoma were 72.5% （37/51） and 60.8% （31/51）, in normal gallbladder mucosa were 5% （1/20） and 20.0% （4/20）, in cholecystitis and gallstone were 11.1% （10/90） and 32.2% （29/90）, respectively. There were significant differences among the three groups in IDO and FOXP3 expressions （P〈0.01）. The positive expression rates of IDO and FOXP3 were 7.1% and 14.3% for simple hyperplasia, 17.7% and 35.3% for atypical hyperplasia, 40% and 35% for gallbladder carcinoma （stages Ⅰ-Ⅲ ）, and 77.4% and 64.5% for gallbladder carcinoma （stages Ⅳ-Ⅴ ）. There were significant differences among the four groups in IDO and FOXP3 expressions （P〈0.01）. There were significant differences among the Nevin stage groups, lymph node metastasis group and gallbladder stone in IDO and FOXP3 expressions. However, there were no significant differences a mong the sex groups and the age groups in IDO and FOXP3 expressions （P〉0.05）. In gallbladdercarcinoma, the expression of IDO had a positive correlation with FOXP3 expression in lymphocyte （r〈0. 406,P=0. 003）. Conclusion In gallbladder cancer, a high-expression of IDO and an expression of FOXP3 in lymphocyte are closely related with immune tolerance of gallbladder carcinoma. The results provide a reference for clinical use of immunotherapy in gallbladder cancer.

关 键 词：原发性胆囊癌 吲哚胺2 3双加氧酶 叉状头转录因子3 

分 类 号：R735.8[医药卫生—肿瘤]