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.

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