Lentinan

Lentinan is a beta-glucan polysaccharide isolated from the shiitake mushroom, Lentinula edodes. It is a high-molecular-weight, water-soluble β-1,3-glucan with β-1,6 side chains. As a member of the fungal beta-glucans, lentinan is classified as an immunomodulatory or biological response modifier rather than a direct cytotoxic agent.

Source and preparation: Lentinan can be obtained from shiitake fruiting bodies or cultured mycelium. Commercial preparations are purified from fungal material and prepared for clinical use, typically by injection.

Mechanism of action: Lentinan acts by modulating the immune system. It binds to receptors on innate immune cells, including dectin-1 and complement receptor 3 (CR3), leading to macrophage and dendritic cell activation. This triggers production of cytokines such as IL-1, IL-6, TNF-α, and IL-12, and enhances natural killer (NK) cell activity and cytotoxic T-cell responses. The resulting immune stimulation can contribute to anti-tumor effects and may augment the efficacy of certain chemotherapies in some cancer settings.

Medical use and regulatory status: In Japan, lentinan has been used as an adjuvant cancer therapy, particularly for gastric cancer and, in some cases, colorectal cancer, often in combination with chemotherapy. Outside Japan, its use is variable and not widely approved as a standard cancer treatment. It is generally administered by injection and is not approved by the U.S. Food and Drug Administration for cancer therapy.

Evidence and conclusions: Clinical trials and meta-analyses have produced mixed results, with some studies suggesting potential survival or response benefits in specific cancers but no conclusive, broad efficacy. Guidelines in many countries do not endorse routine use outside approved indications.