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Reduced infiltration of T-regulatory cells in tumours from mice fed daily with gamma-tocotrienol supplementation
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  • Shonia Subramaniam,
  • Jeya Seela Anandha Rao,
  • Premdass Ramdas,
  • Mei Han Ng,
  • Methil Kannan Kutty,
  • Kanga Rani Selvaduray,
  • Ammu Kutty Radhakrishnan
Shonia Subramaniam
International Medical University
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Jeya Seela Anandha Rao
International Medical University
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Premdass Ramdas
International Medical University
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Mei Han Ng
Malaysian Palm Oil Board
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Methil Kannan Kutty
Lincoln University College
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Kanga Rani Selvaduray
Malaysian Palm Oil Board
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Ammu Kutty Radhakrishnan
Monash University Malaysia
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Abstract

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 (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 sacrificed. Mice (n=6) were sacrificed at specified time-points for various analysis (blood leucocyte, cytokine production, and immunohistochemistry). Tumour volume was measured once every seven 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-gamma (IFN) and lower transforming growth factor-beta (TGF-) levels were noted in the T3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-122R), interleukin-24 (IL-24) and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the T3 fed animals. Gene expression studies showed the downregulation 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 Treg cells in the tumour microenvironment in a syngeneic mouse model of BC.

Peer review status:UNDER REVIEW

11 May 2021Submitted to Clinical & Experimental Immunology
12 May 2021Assigned to Editor
12 May 2021Submission Checks Completed
24 May 2021Reviewer(s) Assigned
13 Jun 2021Review(s) Completed, Editorial Evaluation Pending
13 Jun 2021Editorial Decision: Revise Major
22 Jun 20211st Revision Received
23 Jun 2021Reviewer(s) Assigned