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.

Background Efficient cancer therapy is sought not only for primary tumor treatment but also for the prevention of metastatic cancer growth. Immunotherapy has been shown to prevent cancer metastasis by inducing antigen-specific immune responses. Indocyanine green (ICG) has a peak spectral absorption at about 800 nm, which makes it a photothermal reagent for direct treatment of solid tumors by photothermal therapy (PTT). Since PTT alone cannot fully induce antigen-specific immune response for prevention of cancer metastasis, the combination of PTT and immunotherapy has been developed as a new strategy of cancer treatment. Methods Thermal responsive liposomes (TRL) were synthesized by incorporating ICG into the lipid bilayer and encapsulating the water-soluble immune stimulatory molecule polyinosinic:polycytidylic acid (poly I:C) in the hydrophilic core. The poly I:C- and ICG-containing TRLs (piTRLs) were analyzed according to size, and their photothermal effect was evaluated following laser irradiation at 808 nm. Moreover, the temperature-dependent release of poly I:C was also measured. For cancer therapy, CT-26 (carcinoma) and B16 (melanoma) cells were subcutaneously inoculated to build the 1st transplanted tumor in BALB/c and C57BL/6 mice, respectively. These mice received a 2nd transplantation with the same cancer cells by intravenous inoculation, for evaluation of the anti-metastatic effects of the liposomes after PTT. Results Near-infrared (NIR) laser irradiation increased the temperature of piTRLs and effectively released poly I:C from the liposomes. The increased temperature induced a photothermal effect, which promoted cancer cell apoptosis and dissolution of the 1st transplanted tumor. Moreover, the released poly I:C from the piTRL induced activation of dendritic cells (DCs) in tumor draining lymph node (tdLN). Cancer cell apoptosis and DC-activation-mediated cancer antigen-specific immune responses further prevented growth of lung metastatic cancer developed following intravenous transplantation of cancer cells. Conclusion These results demonstrated the potential usage of a piTRL with laser irradiation for immuno-photothermal therapy against various types of cancer and their metastases. Electronic supplementary material The online version of this article (10.1186/s40425-019-0702-1) contains supplementary material, which is available to authorized users.

Natural polysaccharides have shown immune modulatory effects with low toxicity in both animal and human models. A previous study has shown that the polysaccharide from Codium fragile (CFP) promotes natural killer (NK) cell activation in mice. Since NK cell activation is mediated by dendritic cells (DCs), we examined the effect of CFP on DC activation and evaluated the subsequent induction of anti-cancer immunity in a murine model. Treatment with CFP induced activation of bone marrow-derived dendritic cells (BMDCs). Moreover, subcutaneous injection of CFP promoted the activation of spleen and lymph node DCs in vivo. CFP also induced activation of DCs in tumor-bearing mice, and combination treatment with CFP and ovalbumin (OVA) promoted OVA-specific T cell activation, which consequently promoted infiltration of IFN-γ-and TNF-α-producing OT-1 and OT-II cells into the tumors. Moreover, combination treatment using CFP and cancer self-antigen efficiently inhibited B16 tumor growth in the mouse model. Treatment with CFP also enhanced anti-PD-L1 antibody mediated anti-cancer immunity in the CT-26 carcinoma-bearing BALB/c mice. Taken together these data suggest that CFP may function as an adjuvant in the treatment of cancer by enhancing immune activation.