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.
authors: Seoul Department of Immunology, College of Medicine, Konkuk University, Chungju, South Korea.
authors: Tae Heung
authors: TH
authors: Kang
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors: Jayne
authors: J
authors: Knoff
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors: Wei-Hsi
authors: WH
authors: Yeh
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors: Benjamin
authors: B
authors: Yang
authors: Department of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Chenguang
authors: C
authors: Wang
authors: Seoul Department of Immunology, College of Medicine, Konkuk University, Chungju, South Korea.
authors: Young Seob
authors: YS
authors: Kim
authors: Division of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, South Korea.
authors: Tae Woo
authors: TW
authors: Kim
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors: Tzyy-Choou
authors: TC
authors: Wu
authors: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors: Chien-Fu
authors: CF
authors: Hung
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009569:Nitric Oxide / Q000737:chemistry / Q000633:toxicity; D050725:Papillomavirus E7 Proteins / Q000276:immunology / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D039481:CD11b Antigen; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D009569:Nitric Oxide; D024502:alpha-Tocopherol