Objectives:Innate lymphoid cells (ILCs) and natural killer (NK) cells represent a diverse group of innate immune populations that modulate immune responses and tissue equilibrium across various diseases, including cancer. In the present study, we analyzed single-cell RNA sequencing (scRNA-seq) data to explore the landscape and functional status of ILC subsets in patients with head and neck squamous cell carcinoma (HNSCC).Methods: The GSE164690 dataset, which includes preprocessed scRNA-seq and clinical data, was acquired from the Gene Expression Omnibus database. The Cancer Genome Atlas database was used to develop the survival prediction model.Results: A total of 95,809 immune cells were clustered into 16 immune cell clusters, among which 7278 NK cells were further subdivided into 11 clusters. Among the 11 clusters, eight NK cell clusters, two intraepithelial ILC1 (ieILC1) clusters, and one ieILC1–NK-intermediate (ieILC1-NK-int) cluster were identified. Among the ieILC1/NK clusters, ieILC1-1 exhibited the highest immunological activity and was mainly derived from human papillomavirus-positive samples. Further, ieILC1s showed higher enrichment of pathways related to inflammation and effector functions—such as inflammatory response, interferon-gamma response, and interferon-alpha response—compared to the other clusters. Moreover, we developed prognostic prediction models based on differentially expressed genes in the ieILC1/NK clusters. Risk scores of the ieILC1-1, ieILC1-NK-int, and NK clusters were identified as independent prognostic factors for shorter overall survival (OS) and progression-free survival (PFS). Recursive partitioning revealed that combining ieILC1-1 and the NK clusters strongly predicted shorter OS and PFS.Conclusions: Our findings highlight the diverse landscape and prognostic significance of ieILC1/NK cells in patients with HNSCC.
目的：固有淋巴细胞（ILCs）与自然杀伤（NK）细胞构成了一组多样化的先天免疫群体，在包括癌症在内的多种疾病中调节免疫反应和组织稳态。本研究通过分析单细胞RNA测序（scRNA-seq）数据，探索头颈部鳞状细胞癌（HNSCC）患者中ILC亚群的分布特征及功能状态。 方法：从基因表达综合数据库获取包含预处理scRNA-seq及临床数据的GSE164690数据集，并利用癌症基因组图谱数据库构建生存预测模型。 结果：共95,809个免疫细胞被聚类为16个免疫细胞群，其中7,278个NK细胞进一步细分为11个亚群。这11个亚群包括8个NK细胞簇、2个上皮内ILC1（ieILC1）簇和1个ieILC1-NK中间态（ieILC1-NK-int）簇。在ieILC1/NK细胞簇中，ieILC1-1亚群显示出最高的免疫活性，且主要来源于人乳头瘤病毒阳性样本。进一步分析表明，与其他亚群相比，ieILC1s在炎症反应、干扰素-γ应答及干扰素-α应答等炎症与效应功能相关通路上富集程度更高。基于ieILC1/NK细胞簇的差异表达基因，我们构建了预后预测模型，发现ieILC1-1、ieILC1-NK-int和NK细胞簇的风险评分均可作为总生存期（OS）和无进展生存期（PFS）缩短的独立预后因素。递归分区分析显示，联合ieILC1-1与NK细胞簇能显著预测更短的OS和PFS。 结论：本研究揭示了HNSCC患者中ieILC1/NK细胞的异质性分布及其重要的预后价值。
肿瘤(癌症)患者之家