Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China.
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, South Korea.
Nat Commun. 2020 Mar 4;11(1):1187. doi: 10.1038/s41467-020-15030-4.
Induction of antigen-specific immune activation by the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. In this study, we find that FimH, which is an Escherichia coli adhesion portion, induces toll-like receptor 4-dependent and myeloid differentiation protein 2-independent DC maturation in mice in vivo. A combined treatment regimen with FimH and antigen promotes antigen-specific immune activation, including proliferation of T cells, production of IFN-γ and TNF-α, and infiltration of effector T cells into tumors, which consequently inhibits tumor growth in mice in vivo against melanoma and carcinoma. In addition, combined therapeutic treatment of anti-PD-L1 antibodies and FimH treatment efficiently inhibits CT26 tumor growth in BALB/c mice. Finally, FimH promotes human peripheral blood DC activation and syngeneic T-cell proliferation and activation. Taken together, these findings demonstrate that FimH can be a useful adjuvant for cancer immunotherapy.
通过树突状细胞(DC)的成熟来诱导抗原特异性免疫激活是癌症免疫治疗中使用的一种策略。在本研究中,我们发现大肠杆菌黏附部分 FimH 在体内诱导小鼠 Toll 样受体 4 依赖性和髓样分化蛋白 2 非依赖性 DC 成熟。FimH 与抗原的联合治疗方案促进了抗原特异性免疫激活,包括 T 细胞增殖、IFN-γ 和 TNF-α 的产生,以及效应 T 细胞浸润肿瘤,从而抑制了体内黑色素瘤和癌小鼠的肿瘤生长。此外,抗 PD-L1 抗体和 FimH 联合治疗可有效抑制 BALB/c 小鼠 CT26 肿瘤的生长。最后,FimH 促进人外周血 DC 的激活以及同种 T 细胞的增殖和激活。综上所述,这些发现表明 FimH 可用作癌症免疫治疗的一种有效佐剂。