Abstract
The aim of this study was to evaluate the effectiveness of immunotherapy using dendritic cells (DC) pulsed with tumor lysate (a DC vaccine) in combination with daily supplementation of tocotrienol-rich fraction (TRF) to potentiate anti-tumor immune responses. We had previously reported that DC-vaccine immunotherapy together with TRF supplementation induced protective immunity to tumor challenge. Breast cancer was induced in female BALB/c mice. The mice were randomly assigned into the treatment groups. At autopsy, peripheral blood was collected in heparinized tube and the expression of cell surface molecules (CD40, CD80, CD83, and CD86) that are crucial for T-cell activation and survival were analyzed by flow cytometry. Tumor was excised from each animal and snap-frozen. Total RNA was extracted from each tumor tissue for microarray and gene expression analysis. Total protein was extracted from tumor tissue for protein expression studies using Western blotting. The results show that systemic administration of 1 mg TRF daily in combination with DC-vaccine immunotherapy (DC + TL + TRF) caused a marked reduction (p < 0.05) of tumor size and increased (p < 0.05) the survival rates of the tumor-inoculated mice. The expression of CD40, CD80, CD83, and CD86 were upregulated in peripheral blood from the DC + TL + TRF group compared to other groups. In addition, there was higher expression of FasL in tumor-excised mice from the DC + TL + TRF group compared to other groups. FasL plays an important role in maintaining immune privilege and is required for cytotoxic T-lymphocyte (CTL) activity. Microarray analysis identified several genes involved in the regulation of cancer. In this study, we focused on the special AT rich binding protein 1 (SATB1) gene, which was reported to have dual functions, one of which was to induce aggressive growth in breast cancer cells. Tumors from DC + TL + TRF mice showed lower (p < 0.05) expression of SATB1 gene. Further study will be conducted to investigate the molecular functions of and the role of SATB1 in 4T1 mammary cancer cells and DC. In conclusion, TRF supplementation can potentiate the effectiveness of DC-vaccine immunotherapy.
Highlights
Efforts to find a cure for cancer have been ongoing for some time
We had reported that the combination of Dendritic cells (DC) pulsed with Tumor lysate (TL) (DC + TL) and tocotrienol-rich fraction (TRF) supplementation showed marked anti-tumor effects, as a marked inhibition of tumor growth and metastasis was observed in the mice that received this treatment [21,24]
We compared the effectiveness of un-pulsed DC (DC alone), DC pulsed with TL tumor lysate (DC + TL) and DC + TL with daily
Summary
Efforts to find a cure for cancer have been ongoing for some time. Researchers have used several approaches, including developing vaccines against some tumors such as breast, lung, colon, and prostate cancers [1,2,3,4,5,6,7]. Dendritic cells (DC) represent a key cell used to develop cancer vaccines as this cell is the most potent antigen-presenting cell (APC) [8,9,10], playing a key role in mediating. Vaccines 2019, 7, 198 anti-tumor immune responses. Several studies have demonstrated that tumor antigen-pulsed DC (DC vaccines) can induce activation and proliferation of cytotoxic T-lymphocytes (CTL) and T-helper (Th) cells via antigen presentation by major histocompatibility complex (MHC) class I and class II molecules, respectively, to mediate anti-tumor responses [1,16]. Some studies have shown that addition of adjuvants such as cytokines [20] or micronutrients [21] can boost anti-cancer immune responses initiated by the administration of DC vaccines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
