Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy

大肠杆菌黏附部分FimH可作为癌症免疫疗法的佐剂。

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作者:Wei Zhang # ,Li Xu # ,Hae-Bin Park ,Juyoung Hwang ,Minseok Kwak ,Peter C W Lee ,Guang Liang ,Xiaoyan Zhang ,Jianqing Xu ,Jun-O Jin

Abstract

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.

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