Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma.
Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma.
复制标题
食管鳞状细胞癌免疫浸润的表型分析和预后意义
DOI：
10.1080/2162402x.2021.1883890
复制
发表时间：
2021-02-10
期刊：
影响因子：
7.2
通讯作者：
Wen J
中科院分区：
文献类型：
--
作者：
Pan C;Wang Y;Liu Q;Hu Y;Fu J;Xie X;Zhang S;Xi M;Wen J
摘要食管鳞状细胞癌（ESCC）的肿瘤微环境（TME）影响肿瘤进展，但了解甚少。我们从279例食管切除术后患者中获取了肿瘤组织，并使用多重荧光免疫组织化学（mfMHC）对上皮内和间质区域的TME进行了表征。观察到异质性免疫群体浸润肿瘤和未受累的食管组织。上皮内程序性死亡配体1（PD-L1）阳性肿瘤相关巨噬细胞（TAM）和基质颗粒酶B+激活的细胞毒性T细胞（aCTL）的浸润与延长的总生存期（OS）和无病生存期（DFS）相关。上皮内记忆性T细胞浸润预测OS延长，而上皮内和间质调节性T细胞（Treg）浸润分别与OS和DFS缩短相关。结合免疫浸润和临床病理因素的多变量模型在预测3年和5年OS和DFS方面优于肿瘤淋巴结转移（TNM）分期。Treg的浸润与包括CTL、aCTL和自然杀伤（NK）细胞在内的抗肿瘤效应物的浸润呈负相关。上皮内记忆T细胞浸润也与PD-L1表达呈负相关。在空间分析中，在高PD-L1+ TAM浸润组中，上皮内树突状细胞（DC）-记忆T细胞接合增加。TME的表征揭示了免疫群体之间复杂的相互作用，并可用于对患者进行预后预测和免疫治疗。
ABSTRACT The tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC) impacts tumor progression but is poorly understood. We obtained tumor tissues from 279 patients after esophagectomy and characterized the TME in intraepithelial and stromal regions using multiplex fluorescent immunohistochemistry (mfIHC). A heterogeneous immune population infiltrating tumor and the uninvolved esophageal tissue were observed. The infiltration of intraepithelial programmed death ligand 1 (PD-L1)-positive tumor-associated macrophages (TAMs) and stromal granzyme B+ activated cytotoxic T cells (aCTLs) correlated with both prolonged overall survival (OS) and disease-free survival (DFS). The intraepithelial memory T cell infiltration predicted longer OS, while intraepithelial and stromal regulatory T cell (Treg) infiltration was associated with shortened OS and DFS, respectively. Multivariate models combining immune infiltrates and clinicopathological factors outperformed tumor-node-metastasis (TNM) stage in predicting OS and DFS at 3 and 5 years. The infiltration of Treg inversely correlated with that of the antitumor effectors including CTLs, aCTLs, and natural killer (NK) cells. Intraepithelial memory T cell infiltration also negatively correlated with PD-L1 expression. In spatial analysis, intraepithelial dendritic cell (DC)-memory T cell engagement increased in high PD-L1+ TAM infiltration group. The characterization of the TME revealed a complex interplay between immune populations and may be employed to stratify patient for prognosis prediction and immunotherapy.