Química medicinal

Lentinan, A Shiitake Mushroom β-Glucan, Stimulates Tumor-Specific Adaptive Immunity through PD-L1 Down-Regulation in Gastric Cancer Cells

Abstract

Hiroko Ina, Masahiko Yoneda, Mitsuro Kanda, Yashiro Kodera, Megumi Kabeya, Shu Yuasa, Takae Kataoka, Ryuichi Furuta and Kenji Ina

Background: Despite the significant advances in chemotherapy, the prognosis of unresectable gastric cancer is still very poor and the role of immunotherapy remains to be clarified. We examined whether lentinan, a biological response modifier, could enhance the chemotherapeutic effects.

Materials and methods: A retrospective cohort study was conducted to evaluate the survival benefits of lentinan among the patients with gastric cancer receiving chemotherapy. To investigate the mechanisms underlying the clinical effects of lentinan, its cytotoxic activity was accessed by cell proliferation assay. The expression of molecules relevant to immune checkpoints were analyzed by real-time PCR using human gastric cancer cell lines; MKN1, MKN45, and NUGC3.

Results: The addition of lentinan prolonged the survival of patients with gastric cancer receiving S-1 based chemotherapy. Lentinan reduced the constitutive expression of PD-L1 in all cell lines mainly by suppressing the MAPK pathway.

Conclusion: Lentinan at clinical concentrations stimulates tumor-specific adaptive immunity through PD-L1 downregulation, which may enhance chemotherapy-induced tumor clearance and patient survival.