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Accumulation and suppressive function of regulatory T cells in malignant ascites: Reducing their suppressive function

Zilong Hu1, Shidong Hu1, Youjun Wu1

  • 1Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.

Oncology Letters
|March 20, 2018
PubMed

Insights

Arsenic trioxide (As2O3) reduces immunosuppressive regulatory T cells (Tregs) in malignant ascites. This treatment also enhances the activity of tumor-infiltrating lymphocytes (TILs), potentially improving adoptive cell therapy for gastric cancer.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Adoptive cell therapy (ACT) shows promise but is limited by tumor escape mechanisms like regulatory T cells (Tregs).
  • Malignant ascites in gastric cancer is associated with poor prognosis and immune suppression.
  • Understanding T-cell subsets in ascites is crucial for improving cancer immunotherapy.

Purpose of the Study:

  • To analyze T-cell subsets within malignant ascites lymphocytes.
  • To investigate the in vitro effects of arsenic trioxide (As2O3) on Tregs and ascites-derived tumor-infiltrating lymphocytes (TILs).

Main Methods:

  • Flow cytometry to detect T-cell subsets in ascites.
  • Immunohistochemistry and RT-qPCR to assess Forkhead box P3 (FoxP3) expression.
  • ELISA to measure cytokine levels (IL-10, TGF-β, IFN-γ).

Main Results:

  • Ascites lymphocytes showed a significantly higher frequency of Tregs compared to peripheral blood.
  • In vitro As2O3 treatment reduced Treg numbers and Foxp3 mRNA levels.
  • As2O3 increased IFN-γ and decreased IL-10 and TGF-β levels in ascites-derived TILs.

Conclusions:

  • As2O3 may selectively deplete Tregs and inhibit their immunosuppressive function.
  • As2O3 treatment can enhance the cytotoxic activity of ascites-derived TILs.
  • These findings suggest As2O3 as a potential therapeutic agent to improve ACT efficacy in gastric cancer.
Keywords:
arsenic trioxideimmunotherapymalignant ascitesregulatory T cells

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