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.
Highlights
Induction of antigen-specific immune activation by the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy
As FimH promotes the activation of innate immune cells in vitro and in vivo[23,25], we examined whether it can induce the activation of lymph node (LN) DCs in mice in vivo
FimH was purified from E. coli, and the endotoxin was removed by a column treatment method, as detailed in the “Methods” section (Supplementary Fig. 1)
Summary
Induction of antigen-specific immune activation by the maturation of dendritic cells (DCs) is a strategy used for cancer immunotherapy. 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. 1234567890():,; Immunotherapy is an emerging treatment method for cancer, and includes approaches, such as immune checkpoint blockade antibody (Ab) treatment, chimeric antigen (Ag) receptor T-cell therapy, and cancer vaccines[1,2,3]. Many novel immunotherapy methods are being developed, a combined treatment method of adjuvants and cancer antigens is desirable as a form of traditional immunotherapy This is because a combined adjuvant and Ag treatment reduces unwanted inflammation through Ag-specific immune responses and can be developed as a cancer vaccine[3,4]. DCs are powerful APCs for the promoting Ag-specific adaptive immune activation, including the activation of CD4+ helper T (Th) cells and CD8+ cytotoxic T lymphocytes (CTL)[18,19]
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