Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma
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两种免疫增强分子亚型在晚期头颈鳞状细胞癌的炎症、检查点信号传导和结果方面存在差异
DOI：
10.1080/2162402x.2017.1392427
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Lang, Jinyi
中科院分区：
文献类型：
--
作者：
Cao, Bangrong;Wang, Qifeng;Lang, Jinyi
原发性肿瘤的免疫环境与免疫治疗的临床疗效和获益有关。本研究旨在探讨晚期头颈部鳞状细胞癌（HNSCC）的瘤内免疫特征及其临床意义。来自两个队列（癌症基因组图谱，TCGA，n = 203;莱比锡头颈组，LHNG，n = 198）的401个处于III-IVB期的HNSCC的基因表达谱参与该分析。根据免疫相关基因的总体分布，在HNSCC中发现了4种基因表达亚型（C1-4）。总体而言，C2和C3亚型显示免疫谱上调和肿瘤淋巴细胞浸润增加，表现出增强的免疫微环境（EIME）。然而，两种EIME亚型在免疫标志物和临床特征方面存在差异。C2亚型表现出更高的巨噬细胞签名表达，而C3亚型与B细胞浸润更相关。C2和C3亚型之间T细胞和NK细胞浸润无差异。与C3亚型相比，C2亚型肿瘤的特征在于炎症。虽然检查点受体PD 1和CTLA 4在EIME亚型之间表达相同，但与C3相比，它们的配体（PD-L1/PD-L2，CD 86/CD 80）在C2亚型中显著上调。HPV阳性肿瘤主要富集在亚型C3中，而不是C2中。此外，C2亚型患者的结局比C3亚型患者更差。总之，在晚期HNSCC中鉴定出两种具有不同免疫特征和临床特征的免疫增强亚型。HNSCC亚组之间不同的免疫微环境可能为免疫治疗策略提供新的见解。
ABSTRACT The immune environment of primary tumor is associated with the clinical response and benefit of immunotherapy. This study aims to investigate the intratumoral immune profile and its clinical relevance in advanced head and neck squamous cell carcinoma (HNSCC). Gene expression profiles of 401 HNSCCs at stage III-IVB from two cohorts (The Cancer Genome Atlas, TCGA, n = 203; the Leipzig Head and Neck Group, LHNG, n = 198) were involved in this analysis. Based on the global immune-related genes, four gene expression subtypes (C1-4) were identified in HNSCCs. Overall, subtypes C2 and C3 showed upregulation of immune profiles and increased tumor lymphocyte infiltration, exhibiting an enhanced immune microenvironment (EIME). However, the two EIME subtypes revealed differences in immune markers and clinical features. Subtype C2 showed higher expression of macrophage signature, whereas subtype C3 was more associated with B cell infiltration. T cell and NK cell infiltration was not different between C2 and C3 subtypes. The subtype C2 tumors were characterized by inflammation compared with subtype C3. Although the checkpoint receptors PD1 and CTLA4 expressed equally between the EIME subtypes, their ligands (PD-L1/PD-L2, CD86/CD80) were significantly upregulated in subtype C2 compared with C3. HPV-positive tumors were predominantly enriched in subtype C3 but not in C2. Furthermore, patients in subtype C2 had a worse outcome than those in C3. In summary, two immune-enhanced subtypes with different immune characteristics and clinical features were identified in advanced HNSCC. The different immune microenvironments among HNSCC subgroups may provide new insights into the strategy of immunotherapy.