癌症的恶性特征不仅取决于癌细胞的内在特性，还取决于浸润的免疫细胞的功能。在本研究中，我们旨在研究头颈鳞状细胞癌 (HNSCC) 中免疫细胞的功能状况。我们采用单样本基因集富集分析，根据 29 种免疫细胞功能 (ICF) 来检查 HNSCC 的免疫表型。 TCGA 和 GSE65858 数据集。我们分析了临床特征、免疫微环境、分子谱和生物过程。此外，我们还开发并验证了基于 ICF 的风险评分，用于个性化预后预测。我们使用 qRT-PCR 和免疫组织化学证实了我们队列中 ICF 评分的价值。使用分子对接来预测免疫治疗的潜在化合物。在 769 个 HNSCC 样本中鉴定出三种免疫表型（Immune-L、Immune-M 和 Immune-H）。 Immune-H 的特征与“热”肿瘤一致，Immune-L 与“冷”肿瘤相似，Immune-M 表现出中间特征。 ICF 风险评分与免疫检查点、浸润免疫细胞、肿瘤突变负荷以及对靶向/化疗药物的敏感性相关。基因组变异分析表明高危人群涉及代谢重编程途径。 “肿瘤免疫功能障碍和排除”与“免疫表型评分”算法的结合表明，低风险组从免疫治疗中受益的可能性较高。最后，我们确定了艾曲波帕和其他可能有益于 HNSCC 免疫治疗的化合物。我们的研究为 HNSCC 的肿瘤微环境提供了新的视角，有助于理解 HNSCC 的异质性和个性化/精准医疗的发展。

The malignant characteristics of cancer depend not only on intrinsic properties of cancer cells but also on the functions of infiltrating immune cells. In this study, we aimed to investigate the functional landscape of immune cells in head and neck squamous cell carcinoma (HNSCC).We employed single-sample gene set enrichment analysis to examine the immunophenotypes of HNSCC based on 29 immune cell functions (ICFs) in TCGA and GSE65858 datasets. We analyzed the clinical features, immune microenvironment, molecular profiles, and biological processes. Additionally, we developed and validated an ICF-based risk score for personalized prognosis prediction. We confirmed the value of the ICF score in our cohort using qRT-PCR and immunohistochemistry. Molecular docking was used to predict potential compounds for immunotherapy.Three immunophenotypes (Immune-L, Immune-M, and Immune-H) were identified in 769 HNSCC samples. The characteristics of Immune-H were consistent with a "Hot" tumor, Immune-L was similar to a "Cold" tumor, and Immune-M exhibited intermediate features. The ICF risk score was associated with immune checkpoints, infiltrating immune cells, tumor mutation burden, and sensitivities to targeted/chemotherapeutic agents. Gene set variation analysis implicated the involvement of metabolic reprogramming pathways in the high-risk group. The combination of "Tumor Immune Dysfunction and Exclusion" and "Immunophenoscore" algorithms indicated that the low-risk group had a higher likelihood of benefiting from immunotherapy. Finally, we identified Eltrombopag and other compounds that may be beneficial for HNSCC immunotherapy.Our study provides a novel perspective on the tumor microenvironment of HNSCC, aiding in the understanding of HNSCC heterogeneity and the development of personalized/precision medicine.