Number of genes in different modules.

As an important process in cancer immunotherapy, T cell-mediated tumor killing (TTK) enhances the immune response of patients. However, the role of TTK in Head and Neck Squamous Cell Carcinoma (HNSCC) patients still needs further exploration. Therefore, we comprehensively analyzed the gene expression information and clinical characteristics of 1063 HNSCC in five cohorts. Univariate regression, differential expression analysis, and gene mutation profiling were combined to identify the important genes regulating the sensitivity of tumor cells to T cell-mediated killing (GSTTK) in HNSCC. A total of 20 GSTTK were identified as important genes of HNSCC. Patients were divided into C1 and C2 subgroups (TTK patterns) and displayed significant prognostic differences. Patients with C2 subtype had dismal prognosis characteristic compared to C1 subtype in all validation cohorts. Patients with C1 subgroup exhibited robust immune profile and C1 subgroup patients were significantly enriched in metabolically relevant functions. Notably, the multi-omics analysis found that C1 subgroup have higher mutation burden and C2 subgroup patients had significantly higher copy number variation. Drug sensitivity analysis found that multiple first-line chemotherapeutic drugs were more sensitive in patients with subgroup C1. In conclusion, the establishment of GSTTK provides guidance and assistance to clinicians in the personalized management and treatment of HNSCC patients.

作为癌症免疫治疗的关键过程，T细胞介导的肿瘤杀伤（T cell-mediated tumor killing, TTK）可增强患者的免疫应答。然而，TTK在头颈部鳞状细胞癌（Head and Neck Squamous Cell Carcinoma, HNSCC）患者中的作用仍有待进一步探索。为此，本研究针对5个队列中共计1063例头颈部鳞状细胞癌患者的基因表达信息与临床特征展开了全面分析。通过联合单变量回归分析、差异表达分析与基因突变谱分析，我们筛选出了调控肿瘤细胞对T细胞介导杀伤敏感性的关键基因（GSTTK），最终共鉴定出20个GSTTK关键基因，它们均为头颈部鳞状细胞癌的重要相关基因。研究将患者划分为C1与C2两个亚组（对应不同的TTK模式），两组患者的预后存在显著差异。在所有验证队列中，C2亚型患者的预后均显著差于C1亚型患者。C1亚组患者展现出活跃的免疫表型，且显著富集于代谢相关的生物学功能。值得注意的是，多组学分析结果显示，C1亚组的突变负荷更高，而C2亚组患者的拷贝数变异水平显著更高。药物敏感性分析表明，C1亚组患者对多种一线化疗药物的敏感性更高。综上，本研究构建的GSTTK基因集可为临床医生对头颈部鳞状细胞癌患者实施个性化管理与诊疗提供重要指导与辅助支持。