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伴有或不伴有HPV感染的头颈部鳞状细胞癌肿瘤微环境中免疫细胞浸润和免疫相关基因的特征

Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of HNSCC with or without HPV infection.

作者信息

Zhou Dajie, Wang Jing, Wang Junxin, Liu Xiangdong

机构信息

Department of Clinical Laboratory Center, Yantai Yuhuangding Hospital Yantai 264000, Shandong, China.

Department of Clinical Medicine, Weifang Medical University Weifang 261053, Shandong, China.

出版信息

Am J Transl Res. 2021 Apr 15;13(4):2163-2180. eCollection 2021.

Abstract

Head and neck squamous cell carcinoma (HNSCC) are the sixth most common cancer type in the world. Human papillomavirus (HPV) infection is an emerging risk factor for HNSCC. Immune infiltration of HNSCC is linked to therapeutic results. This article aimed to decide whether variations in HPV status affect immune infiltration, molecular mechanism, and how these results vary in HNSCC patients. We investigated the tumor-infiltrating immune cells (TIICs) and immune-related gene differences between HPV (+) and HPV (-) HNSCC. The gene expression quantification data of HNSCC and their clinical information were download from the TCGA database. Immune-related genes have been linked to the ImmPort platform. After analyzed of 22 TIICs in the HNSCC tumor environment by CIBERSORT and further assessment, lower memory B cell and higher T cell regulatory were connected with better HPV (-) HNSCC outcome, higher activated memory CD4 T cell, higher T cell regulatory, and lower activated NK cell were linked with better HPV (+) result. We finally got five forms of immune genes (CAMP, EDNRB, NTS, CXCL9, LHB) associated with HNSCC progression. Higher expressions of CAMP, EDNRB, and NTS were associated with increased overall survival in HPV (-) patients. Higher expression of CXCL9 and lower expression of LHB contributed to increased overall survival of HPV (+) patients. There tend to be discrepancies in the cell structure of TIICs and immune-related genes in HPV (-) and HPV (+) HNSCC. These variances are typically too crucial for the therapeutic outcome of the patient and the development of the tumor. In specific, our sample established these candidate immune cells and immune-related genes as candidate reservoirs for further researches.

摘要

头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症类型。人乳头瘤病毒(HPV)感染是HNSCC新出现的一个风险因素。HNSCC的免疫浸润与治疗结果相关。本文旨在确定HPV状态的变化是否会影响免疫浸润、分子机制,以及这些结果在HNSCC患者中如何不同。我们研究了HPV(+)和HPV(-)HNSCC之间的肿瘤浸润免疫细胞(TIICs)和免疫相关基因差异。HNSCC的基因表达定量数据及其临床信息从TCGA数据库下载。免疫相关基因已与ImmPort平台相关联。通过CIBERSORT分析HNSCC肿瘤环境中的22种TIICs并进一步评估后,较低的记忆B细胞和较高的调节性T细胞与较好的HPV(-)HNSCC结果相关,较高的活化记忆CD4 T细胞、较高的调节性T细胞和较低的活化自然杀伤细胞与较好的HPV(+)结果相关。我们最终获得了五种与HNSCC进展相关的免疫基因形式(CAMP、EDNRB、NTS、CXCL9、LHB)。CAMP、EDNRB和NTS的高表达与HPV(-)患者总生存期增加相关。CXCL9的高表达和LHB的低表达有助于HPV(+)患者总生存期增加。HPV(-)和HPV(+)HNSCC在TIICs的细胞结构和免疫相关基因方面往往存在差异。这些差异通常对患者的治疗结果和肿瘤的发展至关重要。具体而言,我们的样本将这些候选免疫细胞和免疫相关基因确定为进一步研究的候选库。

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