Treatment of tumors with vitamin e suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects

Tae Heung Kang, Jayne Knoff, Wei Hsi Yeh, Benjamin Yang, Chenguang Wang, Young Seob Kim, Tae Woo Kim, Tzyy Choou Wu, Chien Fu Hung

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.

Original languageEnglish
Article numbere103562
JournalPLoS One
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 29

Fingerprint

suppressor cells
T-cells
Vitamin E
Vitamins
vitamin E
Tumors
vitamins
T-lymphocytes
T-Lymphocytes
neoplasms
Adoptive Transfer
Bearings (structural)
Neoplasms
Tumor Microenvironment
immunotherapy
Immunotherapy
Therapeutics
CD8 Antigens
immunosuppressive agents
immunosuppression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Treatment of tumors with vitamin e suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects. / Kang, Tae Heung; Knoff, Jayne; Yeh, Wei Hsi; Yang, Benjamin; Wang, Chenguang; Kim, Young Seob; Kim, Tae Woo; Wu, Tzyy Choou; Hung, Chien Fu.

In: PLoS One, Vol. 9, No. 7, e103562, 29.07.2014.

Research output: Contribution to journalArticle

Kang, Tae Heung ; Knoff, Jayne ; Yeh, Wei Hsi ; Yang, Benjamin ; Wang, Chenguang ; Kim, Young Seob ; Kim, Tae Woo ; Wu, Tzyy Choou ; Hung, Chien Fu. / Treatment of tumors with vitamin e suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects. In: PLoS One. 2014 ; Vol. 9, No. 7.
@article{1cb3d58926584840afb46f2e77cf1c8b,
title = "Treatment of tumors with vitamin e suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects",
abstract = "Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.",
author = "Kang, {Tae Heung} and Jayne Knoff and Yeh, {Wei Hsi} and Benjamin Yang and Chenguang Wang and Kim, {Young Seob} and Kim, {Tae Woo} and Wu, {Tzyy Choou} and Hung, {Chien Fu}",
year = "2014",
month = "7",
day = "29",
doi = "10.1371/journal.pone.0103562",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Treatment of tumors with vitamin e suppresses myeloid derived suppressor cells and enhances CD8+ T cell-mediated antitumor effects

AU - Kang, Tae Heung

AU - Knoff, Jayne

AU - Yeh, Wei Hsi

AU - Yang, Benjamin

AU - Wang, Chenguang

AU - Kim, Young Seob

AU - Kim, Tae Woo

AU - Wu, Tzyy Choou

AU - Hung, Chien Fu

PY - 2014/7/29

Y1 - 2014/7/29

N2 - Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.

AB - Vitamin E has been shown to have strong anticarcinogenic properties, including antioxidant characteristics, making it an ideal candidate for use in combination with immunotherapies that modify the tumor microenvironment. The tumor microenvironment contains immunosuppressive components, which can be diminished, and immunogenic components, which can be augmented by immunotherapies in order to generate a productive immune response. In the current study, we employ the α-tocopherol succinate isomer of vitamin E to reduce immunosuppression by myeloid derived suppressor cells (MDSCs) as well as adoptive transfer of antigen-specific CD8+ T cells to generate potent antitumor effects against the HPV16 E7-expressing TC-1 tumor model. We show that vitamin E alone induces necrosis of TC-1 cells and elicits antitumor effects in TC-1 tumor-bearing mice. We further demonstrate that vitamin E reverses the suppression of T cell activation by MDSCs and that this effect is mediated in part by a nitric oxide-dependent mechanism. Additionally, treatment with vitamin E reduces the percentage of MDSCs in tumor loci, and induces a higher percentage of T cells, following T cell adoptive transfer. Finally, we demonstrate that treatment with vitamin E followed by E7-specific T cell adoptive transfer experience elicits potent antitumor effects in tumor-bearing mice. Our data provide additional evidence that vitamin E has anticancer properties and that it has promise for use as an adjuvant in combination with a variety of cancer therapies.

UR - http://www.scopus.com/inward/record.url?scp=84904989729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904989729&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0103562

DO - 10.1371/journal.pone.0103562

M3 - Article

C2 - 25072795

AN - SCOPUS:84904989729

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e103562

ER -