Open AccessOral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via mitigation of regulatory T cell‐mediated immunosuppression
Author(s) -
Tanaka Kousuke,
Ishikawa Satoru,
Matsui Yasunori,
Tamesada Makoto,
Harashima Nanae,
Harada Mamoru
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01841.x
Subject(s) - 7,12 dimethylbenz[a]anthracene , ingestion , in vivo , foxp3 , cd8 , melanoma , immune system , spleen , t cell , il 2 receptor , splenocyte , flow cytometry , immunosuppression , biology , medicine , immunology , cancer research , cancer , endocrinology , dmba , carcinogenesis , microbiology and biotechnology
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)‐β. 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)