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

Gamma-tocotrienol (gamma T3) 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 gamma T3 on host T helper (Th) and T regulatory cell (T-reg) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either gamma T3 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 gamma T3 increased CD4(+) (p < 0.05), CD8(+) (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed T-reg cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-gamma and lower transforming growth factor (TGF)-beta levels were noted in the gamma T3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4(+) cells, increased expression of interleukin-12 receptor-beta-2 (IL-12 beta 2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the gamma T3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4(+) T cells isolated from gamma T3-fed mice. Supplementation with gamma T3 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.