唾液腺淋巴上皮癌中PD-L1表达及CD8^(+)T淋巴细胞浸润状况研究  

Programmed death ligand 1 expression and CD8+T lymphocyte infiltration in salivary gland lymphoepithelial carcinoma

作　　者：顾挺[1] 夏荣辉[1] 胡宇华[1] 田臻[1] 王丽珍[1] 张春叶[1] 李江[1] Gu Ting;Xia Ronghui;Hu Yuhua;Tian Zhen;Wang Lizhen;Zhang Chunye;Li Jiang(Department of Oral Pathology,Shanghai Ninth People′s Hospital,Shanghai Jiaotong University School of Medicine College of Stomatology,Shanghai Jiaotong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology,Research Unit of Oral and Maxillofacial Regenerative Medicine,Chinese Academy of Medical Sciences,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院口腔病理科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,中国医学科学院口腔颌面再生医学创新单元,200011

出　　处：《中华病理学杂志》2021年第11期1222-1227,共6页Chinese Journal of Pathology

基　　金：国家自然科学基金(81872187);中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-037)。

摘　　要：目的探讨唾液腺淋巴上皮癌(LEC)中程序性死亡蛋白配体1(PD-L1)在肿瘤细胞及CD8+T淋巴细胞在肿瘤浸润淋巴细胞(TIL)中的浸润状况,分析它们与唾液腺LEC临床病理等指标的相关性。方法收集上海交通大学医学院附属第九人民医院口腔病理科2015—2017年经手术治疗且术后病理确诊为原发性的唾液腺LEC 42例,及2005—2017年经手术治疗且病理确诊为良性淋巴上皮病恶变为LEC即继发性LEC病例21例,应用显色原位杂交和免疫组织化学染色检测EB病毒感染、PD-L1和CD8的表达情况。对PD-L1表达、CD8+T淋巴细胞浸润与唾液腺LEC的类型及临床病理指标之间的关系进行统计学分析。结果 61例(61/63,96.8%)上皮细胞巢中存在EB病毒感染,包括42例(42/42,100%)原发性LEC及19例(19/21,90.5%)继发性LEC。原发性LEC中,PD-L1表达(≥1)率及高表达(≥20)率分别为97.6%(41/42)和78.6%(33/42)。继发性LEC中,PD-L1表达率及高表达率分别为71.4%(15/21)和38.1%(8/21)。PD-L1在唾液腺原发性LEC中的表达率和高表达率均高于继发性LEC(P=0.004,P=0.001)。CD8+T淋巴细胞在原发性及继发性LEC中浸润程度差异无统计学意义(P>0.05)。原发性和继发性LEC中,PD-L1表达与CD8^(+)T淋巴细胞浸润程度均呈正相关(P=0.001,P=0.048)。结论无论是原发性还是继发性唾液腺LEC,均存在较高的PD-L1表达率,其中大部分原发性LEC为PD-L1高表达。LEC中PD-L1表达协同CD8+T淋巴细胞浸润提示大部分患者可能从免疫治疗中获益,其中原发性LEC患者可能获益更明显。Objective To study the expression of programmed death ligand-1(PD-L1)in tumor cells and CD8+T lymphocytes in tumor infiltrating lymphocytes,and to analyze the correlation of PD-L1 expression with infiltration of CD8+T lymphocytes and clinicopathologic features in salivary gland lymphoepithelial carcinoma(LEC).Methods Forty-two cases of primary salivary LECs and 21 cases of secondary salivary LECs were enrolled at the Department of Oral Pathology,Shanghai Ninth People′s Hospital,Shanghai Jiaotong University between 2015 and 2017.The expression of Epstein-Barr(EB)virus,PD-L1 and CD8 was examined using chromogenic in situ hybridization(CISH)and immunohistochemistry(IHC)staining.The data were analyzed using SPSS 23.0 software package.Results EB virus was detected in 61 cases(61/63,96.8%),including 42(42/42,100%)primary LECs and 19(19/21,90.5%)secondary LECs.The PD-L1 positive rate(score≥1)was 97.6%(41/42),and its high-expression rate(score≥20)was 78.6%(33/42)in primary LECs.The PD-L1 positive rate(score≥1)was 71.4%(15/21),and its high-expression rate(≥20)was 38.1%(8/21)in secondary LECs.However,the PD-L1 positive rate(score≥1,P=0.004)and high-expression rate(score≥20,P=0.001)in primary LECs were higher than those in secondary LECs.There was no difference in the infiltration degree of CD8+T lymphocytes between primary and secondary LECs.There was a significant correlation between the expression of PD-L1 and CD8 in primary LECs(P=0.001)and in secondary LECs(P=0.048),respectively.Conclusions There is PD-L1 expression in primary and secondary salivary LECs,while the expression rate is higher in primary LECs than secondary LECs.The combination of PD-L1 expression and CD8^(+)T lymphocytes′presence suggest that most LEC patients might be responsive to immunotherapy,and primary LECs might be more significantly responsive than secondary LECs.

关 键 词：口腔肿瘤 抗原 CD8 免疫组织化学 PD-L1 

分 类 号：R739.87[医药卫生—肿瘤]