Combining a peptide vaccine with oral ingestion of Lentinula edodes mycelia extract enhances anti-tumor activity in B16 melanoma-bearing mice

Abstract

New anticancer vaccines must overcome regulatory T cell (Treg)-mediated immunosuppression. We previously reported that oral ingestion of Lentinula edodes mycelia (L.E.M.) extract restores melanoma-reactive T cells in melanoma-bearing mice via a mitigation of Treg-mediated immunosuppression. In this study, we investigated the effect of oral ingestion of the extract on peptide vaccine-induced anti-tumor activity. The day after subcutaneous inoculation in the footpad with B16 melanoma, mice were freely fed the extract and were vaccinated with a tyrosinase-related protein 2(180-188) peptide. The peptide vaccine was repeated thrice weekly. Melanoma growth was significantly suppressed in mice treated with both the peptide vaccine and L.E.M. extract compared with mice treated with vaccine or extract alone, and the effect was CD8(+) T cell-dependent. The combination therapy increased H-2K(b)-restricted and B16 melanoma-reactive T cells in the draining lymph nodes and spleen. Flow cytometric and immunohistological analyses revealed that the combination therapy significantly decreased the percentage of Tregs in the draining lymph nodes and spleen of melanoma-bearing mice compared to treatment with vaccine or extract alone. Kinetic analyses of peptide-specific T cells and Tregs revealed that induction of peptide-specific T cells by the peptide vaccine alone was transient, but when combined with L.E.M. extract, it efficiently prolonged the duration of peptide-specific T cell induction without increasing the percentage of Tregs. These results indicate that combination therapy enhances peptide vaccine-induced anti-tumor activity due to attenuation of the increase in the percentage of Tregs in tumor-bearing hosts.

Consumption of β-glucans to spice up T cell treatment of tumors: a review

“…Various mice studies also investigated the effects of β-glucan intake on subsets of immune cells within TME, blood or other organs. There were 7 out of 16 studies that reported increased IFN-γ production following ex-vivo stimulation of either blood-derived T cells, splenocytes, cells from tumor or immune tissues, following uptake of β-glucans [106][107][108][110][111][112][113]. In the study where cells from GALT showed increased IFN-γ production following ex-vivo stimulation, authors argued that administered WGP β-glucans induced IL-12 and TNF-α production by DCs and stimulated DC migration into the tumor, which resulted in local expansion of T cells [108].…”

Innovative DNA Vaccine to Break Immune Tolerance Against Tumor Self-Antigen

“…Thus, we have created a vaccination platform technology that is able to break immune tolerance. Other vaccination technologies have been discovered that are also able to break immune tolerance, and it will be of interest to compare them with the technology employed in the current study (O et al, 2003;Yamano et al, 2006;Tanaka et al, 2012;Vasievich et al, 2012).…”

“…Our vaccination technology can potentially be used in conjunction with immune-modulating agents to further enhance the vaccine potency. Previously, Tanaka et al (2012) demonstrates an immune-modulating agent, Lentinula edodes mycelia, mitigating immune suppression by Tregulatory cells can be used to improve TRP2 peptide-based vaccine potency. They demonstrate that TRP2 peptide-based vaccination in conjunction with immune-modulating agent Lentinula edodes mycelia can further enhance the antigenspecific immune response as well as the therapeutic antitumor effect against TRP2-expressing tumors.…”

Induction of Bcl‐xL‐Specific Cytotoxic T Lymphocytes in Mice

“…However, so far, several studies have used model antigens like ovalbumine‐expressing B16 melanoma cells , whereas relatively few endogenous tumour antigens have been characterized and tested in mouse models. Most studies with B16 cells have used gp100 or TRP2 as standard endogenous tumour antigens, whereas many recently defined tumour antigens are less immunogenic . Thus, characterization of new and potent MHC class‐I‐binding CD8 + T‐cell epitopes is essential for further preclinical cancer vaccine development.…”