结直肠癌中LC3与树突状细胞募集、TLS形成的相关性及其临床意义  

Correlation of LC3 and the recruitment of dendritic cell and the formation of TLS in colorectal cancer and its clinical significance

作　　者：武寒 徐磊 王苗苗 张睿哲 许晓阳 郭宁杰 吴淑华[1] WU Han;XU Lei;WANG Miaomiao;ZHANG Ruizhe;XU Xiaoyang;GUO Ningjie;WU Shuhua(Department of Pathology,Binzhou Medical University Hospital,Binzhou 256600,Shandong Province,China)

机构地区：[1]滨州医学院附属医院病理科,山东滨州256600

出　　处：《中国癌症杂志》2023年第9期818-828,共11页China Oncology

基　　金：国家自然科学基金(81772637)。

摘　　要：背景与目的:肿瘤细胞免疫逃逸是肿瘤治疗中的难点,而肿瘤细胞中自噬过度激活会引起肿瘤细胞表面抗原的增加,参与抗肿瘤免疫。本研究通过临床样本检测结直肠癌中自噬关键因子微管相关蛋白轻链3(light chain 3,LC3)表达、成熟树突状细胞(mature dendritic cell,mDC)数目及三级淋巴结构(tertiary lymphoid structure,TLS)的形成,探讨其相关性及临床意义,旨在为增强抗肿瘤免疫治疗提供新思路。方法:采用免疫组织化学EnVision法检测2016年1月—2017年6月滨州医学院附属医院收治的经手术切除的179例T2期高危及T3期结直肠癌患者的癌组织及癌旁组织中LC3、DC-lamp的表达和TLS的形成。采用蛋白质印迹法(Western blot)及实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测TLS+及TLS-结直肠癌组织中LC3、NY-ESO-2、淋巴毒素β(lymphotoxin-beta,LTβ)、CC族趋化因子配体21(CC chemokine ligand 21,CCL21)、CXC族趋化因子配体13(CXC chemokine ligand 13,CXCL13)及白细胞介素17(interleukin-17,IL-17)的表达,分析其相关性及临床意义。采用log-rank检验比较组间预后差异,采用COX比例风险回归模型进行多因素生存分析。结果:结直肠癌组织中LC3、DC-lamp的表达量均高于癌旁组织(P<0.05),LC3与DC-lamp的表达呈正相关(P<0.05)。TLS+组中LC3、NY-ESO-2、LTβ、CXCL13及CCL21的蛋白水平及mRNA表达均高于TLS-组(P<0.05),而IL-17的表达量则低于TLS-组(P<0.05),LC3表达与TLS/生发中心(germinal center,GC)+、TLS/GC-两亚型均呈正相关(P<0.05),且与NY-ESO-2、LTβ、CXCL13及CCL21的表达呈正相关(P<0.05)。DC-lamp在TLS/GC+和TLS/GC-亚型组中的表达量均高于其余两亚组(P<0.05),且呈正相关(P<0.05)。Log-rank检验及COX比例风险回归模型显示,结直肠癌中LC3、DC-lamp、TLS及淋巴结转移与结直肠癌患者的预后密切相关,且均是结直肠癌预后的独立危险因素。结论:结直Background and purpose:It has been recognized as a complex problem in tumor therapy to deal with the tumor immune escape,and over-activated autophagy can cause the increase of tumor surface antigen,which participates in anti-tumor immunity.In this study,the expressions of microtubule-associated protein light chain 3(LC3),mature dendritic cell(mDC)and the formation of tertiary lymphoid structure(TLS),an essential autophagy factor in colorectal cancer,were detected in clinical samples.The results had important clinical implications and provided new insights for enhancing anti-tumor immunity.Methods:Immunohistochemical EnVision method was used to detect the expressions of LC3,DC-lamp and the formation of TLS in cancer tissues and normal mucosal tissues of 179 patients with T2 stage high-risk and T3 stage colorectal cancer who underwent surgical resection at Binzhou Medical University Hospital from January 2016 to June 2017.Western blot and real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)were used to detect the expressions of LC3,NY-ESO-2,lymphotoxin-beta(LTβ),CC chemokine ligand 21(CCL21),CXC chemokine ligand 13(CXCL13)and interleukin-17(IL-17)in TLS+and TLS-colorectal cancer tissues.Then the correlation and clinical significance were analyzed.Log-rank test was used to compare the prognostic differences between groups,and COX proportional risk regression model was used for multivariate survival analysis.Results:Clinical samples showed that the expressions of LC3 and DC-lamp were higher in colorectal cancer tissues than in normal mucosa tissues(P<0.05),and the expressions of LC3 and DC-lamp were positively correlated(P<0.05).The protein and mRNA expressions of LC3,NY-ESO-2,LTβ,CXCL13 and CCL21 were higher in TLS+group than in TLS-group.The expression of IL-17 was higher in the TLS-group than in the TLS+group(P<0.05).The expression of LC3 was positively correlated with TLS/germinal center(GC)+and TLS/GC-subtypes and positively correlated with the expression of NY-ESO-2,LTβ,CXCL13 and CCL21(P<

关 键 词：结直肠肿瘤 轻链3 成熟树突状细胞 三级淋巴结构 临床意义 

分 类 号：R735.35[医药卫生—肿瘤] R735.37[医药卫生—临床医学]