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

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

doi:10.1038/s41467-020-15030-4

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

Nat Commun. 2020 Mar 4;11(1):1187. doi: 10.1038/s41467-020-15030-4.

Authors

Wei Zhang^#¹, Li Xu^#¹, Hae-Bin Park^{1

2}, Juyoung Hwang^{1

2}, Minseok Kwak³, Peter C W Lee⁴, Guang Liang⁵, Xiaoyan Zhang¹, Jianqing Xu¹, Jun-O Jin^{6

7}

Affiliations

¹ Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China.
² Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, South Korea.
³ Department of Chemistry, Pukyong National University, Busan, 48513, South Korea.
⁴ Department of Biomedical Sciences, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505, South Korea.
⁵ Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
⁶ Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China. [email protected].
⁷ Department of Medical Biotechnology, Yeungnam University, Gyeongsan, 38541, South Korea. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adhesins, Escherichia coli / administration & dosage*
Adhesins, Escherichia coli / immunology
Adjuvants, Immunologic / administration & dosage*
Animals
Antineoplastic Agents, Immunological / administration & dosage*
Cell Line, Tumor / transplantation
Cell Proliferation
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Disease Models, Animal
Fimbriae Proteins / administration & dosage*
Fimbriae Proteins / immunology
Humans
Immunotherapy, Adoptive / methods*
Lymphocyte Activation
Mice
Neoplasms / immunology
Neoplasms / pathology
Neoplasms / therapy*
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
Receptors, Chimeric Antigen / immunology
Recombinant Proteins / administration & dosage
Recombinant Proteins / immunology
T-Lymphocytes / immunology
Toll-Like Receptor 4 / metabolism

Substances

Adhesins, Escherichia coli
Adjuvants, Immunologic
Antineoplastic Agents, Immunological
Pdcd1 protein, mouse
Programmed Cell Death 1 Receptor
Receptors, Chimeric Antigen
Recombinant Proteins
Tlr4 protein, mouse
Toll-Like Receptor 4
fimH protein, E coli
Fimbriae Proteins