T 细胞在抗原呈递后需要第二个免疫检查点分子来激活和免疫记忆。我们发现诱导型共刺激剂 (ICOS) 是 B7 免疫检查点共刺激剂 (ICS) 家族中头颈鳞状细胞癌 (HNSCC) 和口腔 SCC (OSCC) 的有利预后因素。本研究分析了癌症基因组图谱 (TCGA) HNSCC 队列、我们的 OSCC 队列和 TCGA 泛癌症数据集中的非 B7 肿瘤坏死因子 (TNF) 超家族 ICS。评估表达、预后和免疫状态的相关性。CD27、CD30、CD40L、死亡结构域 3 (DR3) 和 OX40 的较高表达（可能在 T 细胞表面）定义了 HNSCC 患者更好的总体生存率。此外，CD27、CD30、CD40L、OX40与肿瘤中ICOS表达高度相关。 CD27、CD40L 和 DR3 在 HPV HNSCC 肿瘤中的表达高于 HPV-肿瘤。 CD27/OX40 或 CD27/CD40L/OX40 的组合表达水平能够对小、较少淋巴结受累、早期和 HPV 肿瘤亚群进行有效的生存预测。高表达 CD27、CD30、CD40L、ICOS 和 OX40 的肿瘤表现出增强的免疫细胞浸润。 TCGA 数据集中的绝大多数肿瘤类型也注意到这些 ICS 表达的高度相关性。这项研究的结果不仅证实了 CD27、CD30、CD40L、ICOS 和 OX40 的一致刺激作为癌症免疫治疗的关键策略，同时也激发了对该领域的进一步探索，凸显了癌症治疗的广阔前景。© 2024 中华民国牙科科学协会。 Elsevier B.V. 的出版服务

T cells require second immune checkpoint molecules for activation and immune memory after antigen presentation. We found that inducible co-stimulator (ICOS) has been a favorable prognostic factor amongst B7 immune checkpoint co-stimulators (ICSs) families in head and neck squamous cell carcinoma (HNSCC) and oral SCC (OSCC).This study analyzed the expression of non-B7 tumor necrosis factor (TNF) superfamily ICSs in the Cancer Genome Atlas (TCGA) HNSCC cohort, our OSCC cohort, and TCGA pan-cancer datasets. The correlation in expression, prognosis, and immune status was assessed.The higher expression of CD27, CD30, CD40L, death domain 3 (DR3), and OX40, presumably on the T cell surface, defined better overall survival of HNSCC patients. Besides, CD27, CD30, CD40L, and OX40 were highly correlated with ICOS expression in tumors. CD27, CD40L, and DR3 expression are higher in HPV+ HNSCC tumors than in HPV- tumors. The combined expression level of CD27/OX40 or CD27/CD40L/OX40 enables the potent survival prediction of small, less nodal involvement, early stage, and HPV + tumor subsets. Tumors expressing high CD27, CD30, CD40L, ICOS, and OX40 exhibited enhanced immune cell infiltration. The high correlation in the expression of these ICSs was also noted in the vast majority of tumor types in TCGA datasets.The findings of this study not only confirm the potential of the concordant stimulation of CD27, CD30, CD40L, ICOS, and OX40 as a crucial strategy in cancer immunotherapy but also inspire further exploration into the field, highlighting the promising future of cancer treatment.© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.