Bin-Alee Fardeela, Chunthagonesupawit Nattharee, Meesakul Tamonwan, Diloktaweewattana Areeya, Mahattanasakul Patnarin, Mutirangura Apiwat, Ruangritchankul Komkrit, Keelawat Somboon, Kitkumthorn Nakarin
Faculty of Medicine, Princess of Naradhiwas University, Narathiwat, Thailand.
Master of Science Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Eur J Dent. 2024 Feb;18(1):236-242. doi: 10.1055/s-0043-1764419. Epub 2023 May 2.
4-1BB is a costimulatory immune-activating molecule. Increased amounts of this protein have previously been found in the plasma of patients with oropharyngeal and oral cancer. Here, we focused on this molecule that functions as part of the immune system. We investigated in the peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) of patients with head and neck squamous cell cancer (HNSCC).
The expression level of in the PBMCs was determined using real-time polymerase chain reaction (PCR). The TIMER (Tumor Immune Estimation Resource) web server was utilized to approximate the level in HNSCC TILs. Moreover, 4-1BB immunohistochemistry (IHC) was used to validate TILs in four organs of HNSCC, including oral cancer (OC), oropharyngeal cancer (OPC), sinonasal cancer (SNC), and laryngeal cancer (LC), in both the tumor area and adjacent normal epithelium. The difference in 4-1BB expression levels in various groups was assessed using a Kruskal-Wallis test and an independent sample t-test.
The level of expression in PBMCs was highest in OPC, followed by OC and healthy controls (HC). Significant differences were discovered between HC and OPC and between OC and OPC. Bioinformatics revealed a substantial correlation between expression level and lymphocyte infiltration in HNSCC, including B cells, CD8+ T cells, and CD4+ T cells. IHC validation in HNSCC tissue revealed that the average number of 4-1BB positive TILs in all four HNSCC subtypes was considerably greater than the number of lymphocytes seen in adjacent normal tissue. Interestingly, the number of lymphocytes that were 4-1BB positive increased in relation to the TIL level.
A higher number of expression levels were found in the PBMCs and TILs of HNSCC patients, implying that 4-1BB may be a promising approach for HNSCC patients to improve their immune function. It is important to study and create a treatment that uses 4-1BB medicine as well as existing drugs.
4-1BB是一种共刺激免疫激活分子。此前已发现口咽癌和口腔癌患者血浆中该蛋白含量增加。在此，我们聚焦于这个作为免疫系统一部分发挥作用的分子。我们对头颈部鳞状细胞癌（HNSCC）患者的外周血单核细胞（PBMC）和肿瘤浸润淋巴细胞（TIL）进行了研究。
使用实时聚合酶链反应（PCR）测定PBMC中 的表达水平。利用TIMER（肿瘤免疫评估资源）网络服务器估算HNSCC TIL中的 水平。此外，采用4-1BB免疫组织化学（IHC）方法，对HNSCC四个器官（包括口腔癌（OC）、口咽癌（OPC）、鼻窦癌（SNC）和喉癌（LC））的肿瘤区域和相邻正常上皮中的TIL进行验证。使用Kruskal-Wallis检验和独立样本t检验评估不同组中4-1BB表达水平的差异。
PBMC中 的表达水平在OPC中最高，其次是OC和健康对照（HC）。在HC与OPC之间以及OC与OPC之间发现了显著差异。生物信息学显示，HNSCC中 的表达水平与淋巴细胞浸润（包括B细胞、CD8 + T细胞和CD4 + T细胞）之间存在显著相关性。HNSCC组织中的IHC验证表明，所有四种HNSCC亚型中4-1BB阳性TIL的平均数量明显多于相邻正常组织中的淋巴细胞数量。有趣的是，4-1BB阳性的淋巴细胞数量随TIL水平增加。
在HNSCC患者的PBMC和TIL中发现较高的 表达水平，这意味着4-1BB可能是改善HNSCC患者免疫功能的一种有前景的方法。研究并开发一种使用4-1BB药物以及现有药物的治疗方法很重要。
