Yan Cong, Du Weidong, Kirkwood Keith L, Wang Yao, Zhou Wanhang, Li Zhenning, Tian Yuan, Lin Shanfeng, Zheng Li, Al-Aroomi Maged Ali, Gao Jiaxing, Jiang Sheng, Sun Changfu, Liu Fayu
Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning 110000, PR China.
Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214-8006, USA.
Transl Oncol. 2024 Jun;44:101924. doi: 10.1016/j.tranon.2024.101924. Epub 2024 Mar 2.
Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8 T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8 T cells in TME has not been thoroughly investigated.
A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8 T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments.
CCR7 is knocked out with impaired tumor growth and altered CD8 T cell profiles, revealing the importance of this protein in OSCC.
Inhibition of CCR7 enhances CD8 T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.
头颈癌是全球第六大常见恶性肿瘤，口腔鳞状细胞癌（OSCC）是最常见的头颈癌，是全球癌症发病率和死亡率的主要原因之一。CC趋化因子受体7（CCR7）是一种多功能G蛋白偶联跨膜趋化因子，通过与配体C-C基序趋化因子配体19（CCL19）和C-C基序趋化因子配体21（CCL21）相互作用，影响免疫细胞的趋化性、迁移和癌症进展。大量研究表明CCR7参与多种癌症的恶性进展，反映了CCR7的促癌特性。癌症基因组图谱数据表明CCR7在口腔癌中表达升高。具体而言，肿瘤微环境（TME）中的CCR7表达可能调节一些免疫细胞参与抗肿瘤免疫反应的能力。由于CD8 T细胞已成为关键的免疫治疗靶点，CCR7在TME中初始CD8 T细胞抗肿瘤免疫反应中的作用尚未得到充分研究。
构建CCR7基因敲除小鼠模型，在单细胞RNA测序的指导下，结合体内动物实验和体外细胞实验，验证ccr7对初始CD8 T细胞调节肿瘤微环境的机制。
CCR7被敲除后肿瘤生长受损，CD8 T细胞谱改变，揭示了该蛋白在OSCC中的重要性。
抑制CCR7可增强CD8 T细胞的激活、增殖和抗肿瘤功能，表明其作为治疗靶点的潜力。
