Oral Lentinula edodes mycelia extract enhances the antitumor effect of radiotherapy via gut-associated activation of dendritic and cytotoxic T cells

Abstract Oral administration of Lentinula edodes mycelia extract (L.E.M.) has been shown to stimulate systemic T cell–mediated antitumor immunity and inhibit tumor growth in mice, suggesting its potential to modulate host immune responses. However, the route of this systemic antitumor effect remains unclear. This study focused on gut-associated immune mechanisms by analyzing mesenteric lymph nodes (MLNs), a major component of the gut-associated lymphoid tissue (GALT), and examined whether oral L.E.M. enhances the antitumor efficacy of radiation therapy (RT) in a B16F10-OVA melanoma model. L.E.M. administration upregulated MHC class II and CD86 expression on CD11c + dendritic cells (DCs) in MLNs and significantly increased the proportion of CD103 + subsets, indicating DC maturation within the GALT. In a radiation-induced tumor model, L.E.M. further enhanced DC maturation and increased CD8α + DCs in the spleen, accompanied by elevated effector and central memory fractions of CD8 + T cells in peripheral blood. Antigen-specific CD8 + T cells (OVA tetramer + ) were significantly enriched within tumors, and L.E.M. combined with RT achieved greater tumor growth inhibition than RT alone. These findings demonstrate that oral L.E.M. activates GALT-mediated DC and CD8 + T-cell responses, thereby augmenting the antitumor immune effects of RT.