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

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.

Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model

“…Spleen DCs were further divided into CD8α + and CD8α − DCs, as described by previous studies. 15 , 25 …”

“…CD45.2 + CD8 + and CD45.2 + CD4 + cells with CD3 + cells being defined as the infiltrated OT-1 and OT-II cells, respectively. 15 …”

“… 14 Although these adjuvants induce strong immune activation, they may also elicit undesirable side-effects, including inflammation in healthy tissues owing to toxicity. 15 Moreover, some adjuvants produced from chemical compounds may not completely induce T cell-mediated immune responses, but may elicit an Ab-mediated humoral immune response instead. 16 Lipopolysaccharide (LPS), the outer membrane component of gram-negative bacteria, is the most well-known and strongest type of immune stimulatory molecule, however LPS promotes inflammation in both human and animal models, which may result in sepsis.…”

Alumina Ceramic Exacerbates the Inflammatory Disease by Activation of Macrophages and T Cells

“…FITC-anti-CD3, FITC-anti-CD90.1, FITC-anti-Gr-1, FITC-anti-CD49b, and FITC-anti-TER-119 were used for lineage staining. The cells of CD11c + lineage - in the live leukocytes were defined as cDCs [ 26 ]. The macrophages were defined as CD11c inter CD11b + cells in the splenocytes.…”

“…The pDCs are the main cells that protect body from viral infection and produce interferon-alpha (IFN-α) in responses to the virus [ 23 ]. On the other hand, cDCs and macrophages are representative antigen-presenting cells (APCs) against microbes, which further induce the activation of T and B cells [ 24 , 25 , 26 , 27 ]. The activated DCs and macrophages upregulate co-stimulator, major histocompatibility complex, and pro-inflammatory cytokine production, which promote the differentiation and activation of T cells [ 28 , 29 , 30 ].…”