Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell‐mediated immunosuppression

Abstract

Mitigation of regulatory T cell-mediated immunosuppression is crucial for optimal in vivo anti-tumor immune responses. In this study, we examined the anti-tumor effect induced by oral ingestion of an immunomodulating diet comprised of Lentinula edodes mycelia (L.E.M.) extract. C57BL ⁄ 6 mice were inoculated subcutaneously in the footpad with B16 melanoma and fed L.E.M. extract. Ingestion of L.E.M. extract significantly inhibited tumor growth, and this in vivo anti-tumor effect was not observed in nude mice, suggesting a T cell-dependent mechanism. In addition, ingestion of L.E.M. extract led to significant restoration of H-2K b -restricted and melanoma-reactive T cells in the spleen and draining lymph nodes of melanoma-bearing mice. Flow cytometry analysis revealed that the percentage of Foxp3 + CD4 + T cells increased in spleen and draining lymph nodes in melanoma-bearing mice, but decreased significantly with ingestion of L.E.M. extract. Importantly, selective depletion of CD8 + T cells abolished the L.E.M.-induced anti-tumor effect, whereas that of CD4 + T cells or CD25 + cells showed no additive influence on the effect. Real-time PCR analysis revealed that ingestion of L.E.M. extract by melanoma-bearing mice decreased the level of Foxp3 mRNA within the tumor tissues, and lowered plasma transforming growth factor (TGF)-b. Furthermore, an in vitro assay revealed that an immunosuppressive activity of CD4 + T cells from melanoma-bearing mice was canceled by ingestion of L.E.M. extract. Our results indicate that oral ingestion of L.E.M. extract restores immune responses of class I-restricted and melanoma-reactive CD8 + T cells in melanoma-bearing mice, presumably by a mitigation of regulatory T cells-mediated immunosuppression. (Cancer Sci 2011; 102: 516-521) A nticancer immunotherapy has received considerable attention recently as a new treatment modality. The immune system is capable of recognizing tumor antigens, and cancerreactive cytotoxic T lymphocytes are the most effective cancer destroying cells.(1-3) Although anticancer immunotherapies, including vaccines and adoptive immunotherapy, have been applied clinically, to date their efficacy has been unsatisfactory.(4) One explanation for the insufficient outcome of anticancer immunotherapy trials is the emergence of immunosuppressive cells, including CD4 + CD25 + regulatory T cells (Tregs) and ⁄ or myeloid-derived suppressor cells, in tumor-bearing states.(5,6) The presence of Tregs correlates strongly with unfavorable prognosis. (7,8) Treatment with antibodies or drugs has been proposed as a means of relieving Treg-mediated immunosuppression.(9-14) Nevertheless, safe and widely applicable treatment modalities to mitigate Treg-mediated immunosuppression in cancer patients must be therapeutically beneficial.A dried powder extracted from Lentinula edodes mycelia (L.E.M.) with hot water before germination and after culturing in a medium composed of bagasse and rice bran, (15) has been reported to exhibit anti-tumor activity and immunomodulatory effects in vit...

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Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum

“…In addition, we recently reported that oral ingestion of L.E.M. extract can inhibit the growth of a subcutaneously established B16 melanoma in a T cell-dependent manner via mitigation of Treg-mediated immunosuppression (12). However, the question remains as to how an orally ingested L.E.M.…”

“…C26-inoculated mice, because we previously reported that oral ingestion of L.E.M. can mitigate Treg-mediated immunosuppression in mice bearing a subcutaneously established B16 melanoma (12). We therefore evaluated the percentage of Effects of ingestion of L.E.M.…”

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