Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy.
Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy.
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大肠杆菌粘附部分 FimH 作为癌症免疫治疗的佐剂。
DOI：
10.1038/s41467-020-15030-4
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发表时间：
2020
影响因子：
16.6
通讯作者：
Jin Jun-O
中科院分区：
文献类型：
--
作者：
Zhang Wei;Xu Li;Park Hae-Bin;Hwang Juyoung;Kwak Minseok;Lee Peter C W;Liang Guang;Zhang Xiaoyan;Xu Jianqing;Jin Jun-O
通过树突状细胞 (DC) 的成熟诱导抗原特异性免疫激活是癌症免疫治疗的一种策略。在这项研究中，我们发现FimH（大肠杆菌粘附部分）在小鼠体内诱导Toll样受体4依赖性和骨髓分化蛋白2非依赖性DC成熟。 FimH 和抗原的联合治疗方案可促进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 细胞向肿瘤的浸润，从而抑制小鼠体内黑色素瘤和癌症的肿瘤生长。此外，抗PD-L1抗体和FimH治疗的联合治疗可有效抑制BALB/c小鼠中CT26肿瘤的生长。最后，FimH 促进人外周血 DC 活化和同基因 T 细胞增殖和活化。总而言之，这些发现表明 FimH 可以成为癌症免疫治疗的有用佐剂。
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 anEscherichia coliadhesion 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.