■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,在头颈部鳞状细胞癌(HNSCC)和口腔SCC(OSCC)的B7免疫检查点共刺激因子(ICSs)家族中,诱导型共刺激因子(ICOS)已成为有利的预后因子。
■本研究分析了非B7肿瘤坏死因子(TNF)超家族ICSs在癌症基因组图谱(TCGA)HNSCC队列中的表达,我们的OSCC队列,和TCGA泛癌症数据集。表达的相关性,预后,并评估免疫状态。
■CD27、CD30、CD40L、死亡域3(DR3),和OX40,大概在T细胞表面,确定HNSCC患者的总体生存率更好。此外,CD27,CD30,CD40L,OX40与肿瘤中的ICOS表达高度相关。CD27,CD40L,和DR3在HPV+HNSCC肿瘤中的表达高于在HPV-肿瘤中的表达。CD27/OX40或CD27/CD40L/OX40的联合表达水平使得能够有效预测小、较少的节点参与,早期阶段,和HPV+肿瘤亚群。高表达CD27、CD30、CD40L的肿瘤,ICOS,和OX40表现出增强的免疫细胞浸润。在TCGA数据集中的绝大多数肿瘤类型中也注意到这些ICS的表达的高度相关性。
■这项研究的发现不仅证实了CD27,CD30,CD40L,ICOS,和OX40作为癌症免疫疗法的关键策略,但也激发了对该领域的进一步探索,突出了癌症治疗的前景。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.