帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好，仅出现轻度胃肠道不良事件，并展现出有前景的活性，值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
头颈部鳞状细胞癌患者 PBMCs 和 TIL（肿瘤浸润淋巴细胞）(TILs) 中 4-1BB 高表达
英文原题：High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma.
查看英文原题
High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
在 HNSCC 患者的 PBMCs 和 TILs 中发现了更高数量的 4-1BB 表达水平，这暗示 4-1BB 可能是改善 HNSCC 患者免疫功能的一种有前景的方法。研究和创建一种使用 4-1BB 药物以及现有药物的治疗方法非常重要。
研究思路结论见上方概要
目的
4-1BB是一种共刺激免疫激活分子。此前已在口咽癌和口腔癌患者的血浆中发现该蛋白含量升高。在此，我们聚焦于这一作为免疫系统组成部分发挥作用的分子。我们研究了头颈部鳞状细胞癌（HNSCC）患者外周血单核细胞（PBMCs）和TIL（肿瘤浸润淋巴细胞）（TILs）中的4-1BB。
方法
采用实时聚合酶链反应（PCR）测定PBMCs中4-1BB的表达水平。利用TIMER（肿瘤免疫估计资源）网络服务器估算HNSCC TILs中4-1BB的水平。此外，采用4-1BB免疫组织化学（IHC）验证HNSCC四个器官（包括口腔癌（OC）、口咽癌（OPC）、鼻腔鼻窦癌（SNC）和喉癌（LC））肿瘤区域及邻近正常上皮中的TILs。采用Kruskal-Wallis检验和独立样本t检验评估不同组间4-1BB表达水平的差异。
结果
PBMCs中4-1BB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。生物信息学分析显示，4-1BB表达水平与HNSCC中的淋巴细胞浸润（包括B细胞、CD8+ T细胞和CD4+ T细胞）存在显著相关性。HNSCC组织中的IHC验证显示，所有四种HNSCC亚型中4-1BB阳性TIL的平均数量均显著高于邻近正常组织中观察到的淋巴细胞数量。有趣的是，4-1BB阳性淋巴细胞的数量随TIL水平升高而增加。
展开英文摘要原文
OBJECTIVE
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 4-1BB in the peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) of patients with head and neck squamous cell cancer (HNSCC).
MATERIALS AND METHODS
The expression level of 4-1BB 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 4-1BB 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.
RESULTS
The level of 4-1BB 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 4-1BB 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.
CONCLUSION
A higher number of 4-1BB 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.
论文信息
- 作者
- Bin-Alee F、Chunthagonesupawit N、Meesakul T、Diloktaweewattana A、Mahattanasakul P、Mutirangura A、Ruangritchankul K、Keelawat S
- 第一作者单位
- Faculty of Medicine, Princess of Naradhiwas University, Narathiwat, Thailand.Thailand
- 通讯作者单位
- Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.Thailand
- 期刊
- European journal of dentistry2024 Feb
- 原文标识
- PubMed 37130554 · DOI 10.1055/s-0043-1764419
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →