Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation

Clin Exp Immunol. 2021 Nov;206(2):161-172. doi: 10.1111/cei.13650. Epub 2021 Aug 18.


Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (Treg ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p < 0.05), CD8+ (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed Treg cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4+ T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.

Keywords: T lymphocyte; adaptive immunity; breast cancer; gamma-tocotrienol; mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / immunology
  • Dietary Supplements*
  • Female
  • Killer Cells, Natural / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mammary Neoplasms, Animal / drug therapy
  • Mammary Neoplasms, Animal / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Proteins / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Microenvironment / drug effects*
  • gamma-Tocopherol / pharmacology*


  • Cytokines
  • Neoplasm Proteins
  • gamma-Tocopherol