Rhus Verniciflua Stokes Inhibits PD-1 Expression and Induces Anticancer Effects by Enhancing T Cell Function

Integr Cancer Ther. 2025 Jan-Dec:24:15347354241308220. doi: 10.1177/15347354241308220.

Abstract

Background: Over the last decade, the anticancer effects of Rhus verniciflua Stokes (RVS) have been reported in various preclinical or clinical studies. However, the effects of RVS on immuno-oncology, especially on the functional properties of T cells and their phenotypes, remain unclear. Here, we planned to investigate the impact of RVS on immuno-oncology, specifically focusing on its effects on T cells.

Methods: Peripheral blood mononuclear cells (PBMCs) from breast cancer patients were isolated to obtain cytokine-induced killer cell populations with >85% CD3+ T cells. The anticancer activity of these T cells was evaluated by introducing red fluorescent protein (RFP) into HLA-A02:01 type-matched breast cancer cell lines (MCF7 and MDA-MB-231) and analyzing the results using flow cytometry. The effect of RVS extracts on T cell phenotype was assessed using markers such as CTLA-4 and PD-1, as well as mRNA expression levels of key genes (IFN-γ, TNF-α, and IL-2).

Results: RVS treatment significantly enhanced the anticancer activity of T cells against breast cancer cells. Specifically, T cells treated with 100 µg/mL of RVS showed a 20.6% increase in cytotoxicity against MCF-7 cells and a 36.2% increase against MDA-MB231 cells compared to the control. Additionally, RVS treatment led to a significant reduction in PD-1 expression on T cells.

Conclusion: Our findings demonstrate that RVS treatment enhances T cell function against breast cancer cells by reducing PD-1 expression. These results suggest that components of RVS may serve as potential candidates for restoring exhausted T cells in cancer therapy.

Keywords: PD-1; Rhus verniciflua Stokes; T cell co-culture; anticancer; breast cancer; immuno-oncology.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • CTLA-4 Antigen
  • Cell Line, Tumor
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • MCF-7 Cells
  • Plant Extracts* / pharmacology
  • Programmed Cell Death 1 Receptor*
  • Rhus* / chemistry
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / immunology

Substances

  • Programmed Cell Death 1 Receptor
  • Plant Extracts
  • PDCD1 protein, human
  • Interferon-gamma
  • Interleukin-2
  • CTLA-4 Antigen