CAJ | 학술논문

目的：检测负性共刺激分子PD-L2在人宫颈鳞状细胞癌的表达情况，分析其与患者临床病理特征的相关性，并观察重组人PD-L2蛋白对患者外周血T细胞凋亡的影响。方法采用免疫组织化学染色检测PD-L2蛋白在60例宫颈鳞状细胞癌患者癌组织中的表达，并统计分析PD-L2蛋白表达与宫颈鳞状细胞癌患者临床病理特征的相关性。将患者外周血T淋巴细胞分为空白对照组、PD-L2组和PD-L2＋抗PD-1组单克隆抗体组，流式细胞术分析各组T细胞的凋亡率。结果宫颈鳞状细胞癌表达PD-L2的阳性率为53．3％（32／60）。PD-L2的表达与宫颈鳞状细胞癌的淋巴结转移相关（P＜0．05）。PD-L2组宫颈鳞状细胞癌患者外周血活化CD4＋ T和CD8＋ T的凋亡率分别为17．0％和22．4％，明显高于空白对照组9．0％和16．2％；加入抗PD-1阻断PD-L2与T淋巴细胞、PD-1结合后，PD-L2＋抗PD-1组CD4＋ T和CD8＋ T淋巴细胞凋亡率下降到11．1％和17．5％。结论宫颈鳞状细胞癌细胞异常表达PD-L2，且与肿瘤的淋巴结转移有关。PD-L2通过促进 T 细胞凋亡而削弱宫颈微环境的抗肿瘤免疫，并促进肿瘤的淋巴结转移。PD-L2／PD-1途径有可能成为宫颈鳞状细胞癌免疫治疗的靶点之一。
목적：검측부성공자격분자PD-L2재인궁경린상세포암적표체정황，분석기여환자림상병리특정적상관성，병관찰중조인PD-L2단백대환자외주혈T세포조망적영향。방법채용면역조직화학염색검측PD-L2단백재60례궁경린상세포암환자암조직중적표체，병통계분석PD-L2단백표체여궁경린상세포암환자림상병리특정적상관성。장환자외주혈T림파세포분위공백대조조、PD-L2조화PD-L2＋항PD-1조단극륭항체조，류식세포술분석각조T세포적조망솔。결과궁경린상세포암표체PD-L2적양성솔위53．3％（32／60）。PD-L2적표체여궁경린상세포암적림파결전이상관（P＜0．05）。PD-L2조궁경린상세포암환자외주혈활화CD4＋ T화CD8＋ T적조망솔분별위17．0％화22．4％，명현고우공백대조조9．0％화16．2％；가입항PD-1조단PD-L2여T림파세포、PD-1결합후，PD-L2＋항PD-1조CD4＋ T화CD8＋ T림파세포조망솔하강도11．1％화17．5％。결론궁경린상세포암세포이상표체PD-L2，차여종류적림파결전이유관。PD-L2통과촉진 T 세포조망이삭약궁경미배경적항종류면역，병촉진종류적림파결전이。PD-L2／PD-1도경유가능성위궁경린상세포암면역치료적파점지일。
Objective To determine PD-L2 expression in human cervical squamous cell carcinomas and analyze its association with the clinical and pathologic characteristics of these cases ;observe the role of recombinant PD-L2 protein on apoptosis of active peripheral blood T lymphocytes of cervical carcinoma patients .Methods PD-L2 expression in cervical squamous cell carcinomas was determined by immunohistochemistry staining ,and the association between PD-L2 expression with the clinical and pathologic characteristics of these cases was analyzed .In vitro ,the peripheral blood T lymphocytes of cervical carcinoma patients were divided into blank group ,PD-L2 group and PD-L2+anti-PD-1 group respectively .After these active T cells were cultured 72 h ,their apop-totic rates were detected by flow cytometry .Results PD-L2 expressed in 53 .3% (32/60)cervical squamous cell carcinomas ,and it′s expression associated with lymph node metastasis of these cases (P< 0 .05) .In vitro ,PD-L2 promoted apoptosis of CD4+ T and CD8+ T lymphocytes ,the apoptotic rates were 17 .0% and 22 .4% respectively ,which were higher than 9 .0% and 16 .2% of blank group;however ,the apoptotic rates dropped to 11 .1% and 17 .5% in PD-L2+anti-PD-1 group .Conclusion PD-L2 aberrantly ex-presses in cervical squamous cell carcinomas and is associated with their lymph node metastasis .PD-L2 promotes apoptosis of T lymphocytes and depresses the anti-tumor immunity of cervical microenvironment ,and promotes lymph node metastasis of these cancers .PD-L2/PD-1 pathway may be a potential immunotherapy target of cervical squamous cell carcinomas .