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评估切除的非小细胞肺癌中的肿瘤浸润淋巴细胞、吲哚胺 2,3-双加氧酶-1 和 PD-L1:具有临床病理和预后意义的免疫组织化学研究。

Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications.

机构信息

Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy.

Department of Experimental Medicine, University of Perugia, Perugia, Italy.

出版信息

Virchows Arch. 2019 Feb;474(2):159-168. doi: 10.1007/s00428-018-2483-1. Epub 2018 Nov 17.

Abstract

Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC. One hundred ninety-three NSCLC surgical specimens, formalin-fixed, and paraffin-embedded were assessed for TILs density, TILs localization, IDO-1 (clone 4.16H1), and PD-L1 (clone E1L3N) immunohistochemical expressions. This data was correlated with clinicopathological parameters, disease free, and overall survivals. IDO-1 and PD-L1 high expressions were related to the solid pattern of adenocarcinomas (respectively p = 0.036 and p = 0.026); high PD-L1 expression was correlated with squamous histotype (p = 0.048). IDO-1 overexpression correlated with former smokers (p = 0.041), higher adenocarcinoma stages (p = 0.039), and with both higher TILs density and PD-L1 expression (respectively p = 0.025 and p = 0.0003). A better prognosis was associated with TILs intratumoral or mixed localizations (p = 0.029). TILs localization affects NSCLC prognosis; the higher expression of IDO-1 and PD-L1 in poorly differentiated and more aggressive lung adenocarcinomas, as well as the correlation between high PD-L1 expression and squamous cell histotype, confirm the more efficient immunoescaping of these NSCLC subgroups.

摘要

几种癌症,尤其是非小细胞肺癌(NSCLC),能够逃避肿瘤浸润淋巴细胞(TILs)的免疫监视;其中涉及的分子包括吲哚胺 2,3-双加氧酶 1(IDO-1)和程序性细胞死亡配体-1(PD-L1)。在当前的免疫治疗时代,这些方面非常重要,因此本研究分析了 NSCLC 中 TILs、IDO-1 和 PD-L1 的相互作用及其与临床病理参数和预后的相关性。评估了 193 例福尔马林固定、石蜡包埋的 NSCLC 手术标本的 TILs 密度、TILs 定位、IDO-1(克隆 4.16H1)和 PD-L1(克隆 E1L3N)免疫组织化学表达。将这些数据与临床病理参数、无病和总生存率相关联。IDO-1 和 PD-L1 的高表达与腺癌的实性模式有关(分别为 p=0.036 和 p=0.026);PD-L1 高表达与鳞癌组织类型相关(p=0.048)。IDO-1 过表达与曾经吸烟者相关(p=0.041),腺癌分期较高(p=0.039),以及 TILs 密度和 PD-L1 表达较高(分别为 p=0.025 和 p=0.0003)。更好的预后与 TILs 的肿瘤内或混合定位相关(p=0.029)。TILs 的定位影响 NSCLC 的预后;在分化较差和侵袭性较强的肺腺癌中 IDO-1 和 PD-L1 的高表达,以及 PD-L1 高表达与鳞状细胞组织类型之间的相关性,证实了这些 NSCLC 亚组的免疫逃避更为有效。

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