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[胰腺导管腺癌的肿瘤免疫相关病理特征及其临床意义]

[Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma].

作者信息

Wang C M, Xu C Y, Jiang S, Zhou Q, Jiang Z J, Cheng G P, Wu M J, Feng T T, Yin W J

机构信息

Department of Pathology, the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China.

Department of Oncology, the First Clinical School of Wenzhou Medical University, Wenzhou 325035, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2022 May 8;51(5):419-424. doi: 10.3760/cma.j.cn112151-20210902-00641.

Abstract

To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3T cells were deficient in 124 cases (124/192, 66.31%). CD8T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (=0.035), perineural invasion (=0.002), stage (=0.004) and long-term alcohol consumption (=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (=0.002), and negatively with tumor differentiation (=0.024). CD8T cells were positively correlated with CD3T cells =0.032), MHC-Ⅰ expression (<0.001) and PD-L1 expression (=0.001), and negatively correlated with long-term smoking (=0.016). Univariate analysis showed that histological nonspecific type (=0.013) and TII-N (<0.001) were the factors for good prognosis. Vascular invasion (=0.032), perineural invasion (=0.001), high stage (=0.003) and long-term alcohol consumption (=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

摘要

探讨胰腺导管腺癌(PDAC)中肿瘤免疫相关病理特征及临床意义。收集了2010年1月至2020年12月中国科学院大学附属肿瘤医院192例PDAC患者的所有病理资料和临床信息。评估肿瘤免疫微环境相关形态学特征,采用免疫组织化学(IHC)检测MHC-Ⅰ、PD-L1、CD3和CD8表达。然后分析这些因素之间的相关性及其对预后的影响。其中非特异性腺癌163例(163/192,84.90%),腺鳞癌18例(18/192,9.37%),其他罕见亚型11例(11/192,5.73%)。110例(110/192,57.29%)观察到神经侵犯,86例(86/192,44.79%)观察到血管侵犯。84例(84/182,46.15%)存在严重慢性炎症。52例(52/192,27.08%)肿瘤浸润免疫细胞数量(TII-N)增加。60例(60/192,31.25%)以淋巴细胞和浆细胞为主要浸润免疫细胞,34例(34/192,17.71%)肿瘤主要由粒细胞浸润,98例(98/192,51.04%)表现为混合浸润。124例(124/192,66.31%)CD3T细胞缺乏。152例(152/192,79.58%)CD8T细胞缺乏。156例(156/192,81.25%)MHC-Ⅰ表达下调,46例(46/192,23.96%)PD-L1阳性(CPS≥1)。统计分析显示,TII-N与血管侵犯(=0.035)、神经侵犯(=0.002)、分期(=0.004)和长期饮酒(=0.039)呈负相关。免疫细胞类型与慢性胰腺炎(=0.002)呈正相关,与肿瘤分化(=0.024)呈负相关。CD8T细胞与CD3T细胞(=0.032)、MHC-Ⅰ表达(<0.001)和PD-L1表达(=0.001)呈正相关,与长期吸烟(=0.016)呈负相关。单因素分析显示,组织学非特异性类型(=0.013)和TII-N(<

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