Changes in Indoleamine 2,3-Dioxygenase 1 Expression and CD8+Tumor-Infiltrating Lymphocytes after Neoadjuvant Chemoradiation Therapy and Prognostic Significance in Esophageal Squamous Cell Carcinoma
Changes in Indoleamine 2,3-Dioxygenase 1 Expression and CD8+Tumor-Infiltrating Lymphocytes after Neoadjuvant Chemoradiation Therapy and Prognostic Significance in Esophageal Squamous Cell Carcinoma
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食管鳞癌新辅助放化疗后吲哚胺2,3-双加氧酶1表达及CD8肿瘤浸润淋巴细胞的变化及预后意义
DOI：
10.1016/j.ijrobp.2020.01.020
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发表时间：
2020-09-01
影响因子：
7
通讯作者：
Xi, Mian
中科院分区：
文献类型：
--
作者：
Zhou, Sha;Yang, Hong;Xi, Mian
目的：尽管有良好的临床前证据，但关于新辅助放化疗（CRT）对食管癌免疫标志物表达影响的临床数据有限。本研究旨在评估新辅助CRT后吲哚胺2，3-双加氧酶1（IDO 1）表达、程序性细胞死亡配体1（PD-L1）表达和CD 8+肿瘤浸润淋巴细胞状态的变化及其在食管鳞状细胞癌（ESCC）中的预后意义。在2003年至2017年期间，纳入了138例接受新辅助CRT和食管切除术但未达到病理完全缓解的ESCC患者进行分析。免疫组化IDO 1、PD-L1和CD 8密度进行了分析。结果：在82例配对样本中，IDO 1和PD-L1的表达水平和CD 8密度在新辅助CRT后显著增加（P <0.01）。CRT后IDO 1高表达患者的总生存率（P = 0.001）和无复发生存率（P <0.001）低于IDO 1低表达患者。CRT后高CD 8密度与更有利的总生存率（P = 0.01）和无复发生存率（P = 0.008）显著相关。CRT前后PD-L1表达均不是生存的独立预后因素。分层分析显示，CRT后IDO 1低表达和CD 8高密度患者的生存率显著高于其他亚组。在一个独立的验证cohol.Conclusions：IDO 1和PD-L1的表达和CD 8密度显着增加后，新辅助CRT ESCC的主要结果是可重复的。CRT后IDO 1表达和CD 8密度可作为生存的预后生物标志物。(C)2020作者（S）爱思唯尔公司出版
Purpose: Despite good preclinical evidence, clinical data on the effect of neoadjuvant chemoradiation therapy (CRT) on expression of immune markers in esophageal cancer are limited. This study aimed to evaluate the changes in indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, and CD8+ tumor-infiltrating lymphocyte status after neoadjuvant CRT and the prognostic significance in esophageal squamous cell carcinoma (ESCC).Methods and Materials: Between 2003 and 2017, 138 patients with ESCC who underwent neoadjuvant CRT and esophagectomy without achieving pathologic complete response were included for analysis. Both pre-CRT biopsies and post-CRT surgical specimens were available in 82 patients Immunohistochemistry of IDO1, PD-L1, and CD8 density were analyzed.Results: Among 82 paired samples, the expression levels of IDO1 and PD-L1 and CD8 density increased significantly after neoadjuvant CRT (P < .01 for all). Patients with high IDO1 expression after CRT had poorer overall survival (P = .001) and recurrence-free survival (P < .001) than those with low IDO1 expression. High post-CRT CD8 density was significantly correlated with more favorable overall survival (P = .01) and recurrence-free survival (P = .008). Neither pre- nor post-CRT PD-L1 expression was an independent prognostic factor for survival. Stratification analysis revealed that patients with combined low IDO1 expression and high CD8 density after CRT were significantly associated with better survival than other subgroups. The major findings were reproducible in an independent validation cohort.Conclusions: IDO1 and PD-L1 expression and CD8 density increased significantly after neoadjuvant CRT in ESCC. The post-CRT IDO1 expression and CD8 density could serve as prognostic biomarkers for survival. (C) 2020 The Author(s). Published by Elsevier Inc.