Cao Bangrong, Wang Qifeng, Zhang Huan, Zhu Guiquan, Lang Jinyi
Department of Basic Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Radiation Oncology, and Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Oncoimmunology. 2017 Nov 6;7(2):e1392427. doi: 10.1080/2162402X.2017.1392427. eCollection 2018.
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.
原发性肿瘤的免疫环境与免疫治疗的临床反应和疗效相关。本研究旨在调查晚期头颈部鳞状细胞癌（HNSCC）的肿瘤内免疫特征及其临床相关性。本分析纳入了来自两个队列（癌症基因组图谱，TCGA，n = 203；莱比锡头颈组，LHNG，n = 198）的401例III-IVB期HNSCC的基因表达谱。基于全球免疫相关基因，在HNSCC中鉴定出四种基因表达亚型（C1-4）。总体而言，C2和C3亚型显示免疫特征上调且肿瘤淋巴细胞浸润增加，呈现出增强的免疫微环境（EIME）。然而，这两种EIME亚型在免疫标志物和临床特征方面存在差异。C2亚型显示巨噬细胞特征的表达较高，而C3亚型与B细胞浸润更相关。C2和C3亚型之间的T细胞和NK细胞浸润没有差异。与C3亚型相比，C2亚型肿瘤的特征是炎症。尽管检查点受体PD1和CTLA4在EIME亚型之间表达相当，但与C3相比，它们的配体（PD-L1/PD-L2，CD86/CD80）在C2亚型中显著上调。HPV阳性肿瘤主要富集于C3亚型而非C2亚型。此外，C2亚型患者的预后比C3亚型患者更差。总之，在晚期HNSCC中鉴定出了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。
