Arbutin overcomes tumor immune tolerance by inhibiting tumor programmed cell death-ligand 1 expression

Int J Med Sci. 2024 Nov 11;21(15):2992-3002. doi: 10.7150/ijms.92419. eCollection 2024.

Abstract

Arbutin, predominantly derived from the bearberry plant, exhibits promising immunomodulatory properties. Given its ability to influence the programmed cell death-ligand 1/ programmed cell death-1 (PD-L1/PD-1) pathway, it is emerging as a potential alternative treatment for cancer. A reduced expression of PD-L1, as seen after arbutin treatment, can bolster immune responses critical step in effective tumor immunotherapy. However, the molecular mechanism by which arbutin inhibits PD-L1 is still incompletely known. The expression of PD-L1 was decreased after tumor cells were treated with arbutin. Arbutin can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The findings suggest the protective role of arbutin and provide novel insights into immunotherapy, which involves inhibiting the AKT/mTOR signaling pathway. Arbutin might serve as a potential therapeutic agent alone or in combination with other treatments.

Keywords: Arbutin; programmed cell death protein ligand-1; tumor immune tolerance.

MeSH terms

  • Animals
  • Arbutin* / pharmacology
  • Arbutin* / therapeutic use
  • B7-H1 Antigen* / antagonists & inhibitors
  • B7-H1 Antigen* / metabolism
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immune Tolerance / drug effects
  • Immunotherapy / methods
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / immunology
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • B7-H1 Antigen
  • Arbutin
  • TOR Serine-Threonine Kinases
  • CD274 protein, human
  • Proto-Oncogene Proteins c-akt
  • MTOR protein, human