(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.
(1) 背景:罕见免疫细胞亚型在多种实体肿瘤(尤其是头颈部鳞状细胞癌)中的作用尚未明确。本研究旨在评估头颈部鳞状细胞癌中常见与罕见免疫细胞亚型比例与患者生存结局的关联性。(2) 方法:本队列研究基于CIBERSORT算法与LM22特征矩阵,采用反卷积计算方法,从癌症基因组图谱中517例未经治疗的HPV阴性头颈部鳞状细胞癌患者样本中推断免疫细胞亚型比例。通过单变量与多变量生存分析,将免疫细胞比例与临床、病理及基因组数据进行整合分析。(3) 结果:在多数患者中成功反卷积出22种免疫细胞亚型,其中最常见的免疫细胞类型为M0型巨噬细胞、M2型巨噬细胞及静息记忆性CD4 T细胞。多变量分析显示,晚期N分期及γδ T细胞的存在是生存预后不良的独立预测因素。(4) 结论:本研究发现肿瘤微环境中的γδ T细胞是未经治疗头颈部鳞状细胞癌患者生存的负向预测因子。该结果提示需进一步探究γδ T细胞在头颈部鳞状细胞癌中的作用机制(包括潜在的促肿瘤发生机制),并明确其存在是否可作为选择替代治疗方案的预测指标。