免疫疗法
头颈部鳞状细胞癌
免疫系统
肿瘤微环境
医学
间质细胞
癌症研究
肿瘤科
生物标志物
病理
内科学
基底细胞
渗透(HVAC)
头颈部癌
CD8型
免疫学
生物
癌症
生物化学
作者
Xinhai Zhang,Mengqi Shi,Tie-Lou Chen,Boxin Zhang
标识
DOI:10.1016/j.omtn.2020.08.030
摘要
The tumor microenvironment (TME) chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with the stromal component. A recent clinical trial has shown that the tumor immune cell infiltration (ICI) is correlated with the sensitivity to immunotherapy and the head and neck squamous cell carcinoma (HNSC) prognosis. However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Herein, we proposed two computational algorithms to unravel the ICI landscape of 1,029 HNSC patients. Three ICI patterns were defined, and the ICI scores were determined by using principal-component analysis. A high ICI score was characterized by an increased tumor mutation burden (TMB) and the immune-activating signaling pathways. Activation of transforming growth factor-β (TGF-β) and WNT signaling pathways were observed in low ICI score subtypes, indicating T cell suppression, and may be responsible for poor prognosis. Two immunotherapy cohorts confirmed patients with higher ICI scores demonstrated significant therapeutic advantages and clinical benefits. This study demonstrated that the ICI scores serve as an effective prognostic biomarker and predictive indicator for immunotherapy. Evaluating the ICI patterns of a larger cohort of samples will extend our understanding of TME, and it may provide directions to the current research investigations on immunotherapeutic strategies for HNSC. The tumor microenvironment (TME) chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with the stromal component. A recent clinical trial has shown that the tumor immune cell infiltration (ICI) is correlated with the sensitivity to immunotherapy and the head and neck squamous cell carcinoma (HNSC) prognosis. However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Herein, we proposed two computational algorithms to unravel the ICI landscape of 1,029 HNSC patients. Three ICI patterns were defined, and the ICI scores were determined by using principal-component analysis. A high ICI score was characterized by an increased tumor mutation burden (TMB) and the immune-activating signaling pathways. Activation of transforming growth factor-β (TGF-β) and WNT signaling pathways were observed in low ICI score subtypes, indicating T cell suppression, and may be responsible for poor prognosis. Two immunotherapy cohorts confirmed patients with higher ICI scores demonstrated significant therapeutic advantages and clinical benefits. This study demonstrated that the ICI scores serve as an effective prognostic biomarker and predictive indicator for immunotherapy. Evaluating the ICI patterns of a larger cohort of samples will extend our understanding of TME, and it may provide directions to the current research investigations on immunotherapeutic strategies for HNSC.
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