Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Oncoimmunology. 2020 Apr 14;9(1):1748991. doi: 10.1080/2162402X.2020.1748991. eCollection 2020.
The immunoregulatory protein B7-H3, a member of the B7 family, has been confirmed to be highly expressed in colon cancer. However, the exact influence of B7-H3 on the features and antitumor ability of γδT cells in colon cancer remains unknown. In the present study, we investigated that the proportions of B7-H3 γδT cells were distinctly increased in the peripheral blood and tumor tissues of colon cancer patients. B7-H3 blockade or knockdown promoted proliferation, inhibited cell apoptosis and induced the expression of activation markers (CD25 and CD69) on Vδ2 T cells. In contrast, treatment with the B7-H3 agonist 4H7 had the opposite effect. Furthermore, B7-H3 suppressed IFN-γ expression by inhibiting T-bet in Vδ2 T cells. Moreover, B7-H3 mediated the inhibition of Vδ2 T cell cytotoxicity via the downregulation of IFN-γ and perforin/granzyme B expression. More importantly, blocking the B7-H3 function significantly enhanced the cytotoxicity of Vδ2 T cells against colon cancer cells in vivo. Therefore, the inhibition or blockade of B7-H3 is a potential immunotherapeutic approach for colon cancer.
免疫调节蛋白 B7-H3 是 B7 家族的成员之一，已被证实在结肠癌中高度表达。然而，B7-H3 对结肠癌中 γδT 细胞的特征和抗肿瘤能力的确切影响尚不清楚。在本研究中，我们发现结肠癌患者的外周血和肿瘤组织中 B7-H3 γδT 细胞的比例明显增加。B7-H3 阻断或敲低促进了 Vδ2 T 细胞的增殖，抑制了细胞凋亡，并诱导了活化标志物（CD25 和 CD69）的表达。相比之下，B7-H3 激动剂 4H7 则产生相反的效果。此外，B7-H3 通过抑制 Vδ2 T 细胞中的 T-bet 来抑制 IFN-γ 的表达。此外，B7-H3 通过下调 IFN-γ 和穿孔素/颗粒酶 B 的表达来介导 Vδ2 T 细胞细胞毒性的抑制。更重要的是，阻断 B7-H3 的功能显著增强了 Vδ2 T 细胞对体内结肠癌细胞的细胞毒性。因此，抑制或阻断 B7-H3 是治疗结肠癌的一种潜在免疫治疗方法。
