Modulatory effects of supplementation of Lentinula edodes mycelia extract and l‐arginine on the therapeutic efficacy of immunogenic chemotherapy in colon cancer‐bearing mice

Abstract Some chemotherapeutic drugs can induce cancer cell death and enhance antitumor T‐cell immunity in cancer‐bearing hosts. Immunomodulatory reagents could augment such chemotherapy‐induced effects. We previously reported that oral digestion of Lentinula edodes mycelia (L.E.M.) extract or l ‐arginine supplementation can augment antitumor T‐cell responses in cancer‐bearing mice. In this study, the effects of L.E.M. extract with or without l ‐arginine on the therapeutic efficacy of immunogenic chemotherapy by 5‐fluorouracil (5‐FU)/oxaliplatin (L‐OHP) and/or cyclophosphamide (CP) are examined using two mouse colon cancer models. In MC38 and CT26 cancer models, therapy with 5‐FU/L‐OHP/CP significantly suppressed tumor growth, and supplementation with L.E.M. extract halved the tumor volumes. However, the modulatory effect of L.E.M. extract was not significant. In the CT26 cancer model, supplementation with L.E.M. extract and l ‐arginine had no clear effect on tumor growth. In contrast, their addition to chemotherapy halved the tumor volumes, although the effect was not significant. There was no difference in the cytotoxicity of tumor‐specific cytotoxic T cells generated from CT26‐cured mice treated by chemotherapy alone versus chemotherapy combined with L.E.M. extract/ l ‐arginine. These results indicate that the antitumor effects of immunogenic chemotherapy were too strong to ascertain the effects of supplementation of L.E.M. extract and l ‐arginine, but these reagents nonetheless have immunomodulatory effects on the therapeutic efficacy of immunogenic chemotherapy in colon cancer‐bearing mice.