title: α-TEA as a stimulator of tumor autophagy and enhancer of antigen cross-presentation.
abstract: Stimulation of apoptosis has been reported as the primary mechanism of tumor cell death induced by alpha-tocopheryloxyacetic acid (α-TEA), an esterase-resistant, semi-synthetic derivative of vitamin E (R-R-R-α-tocopherol). New information now shows that α-TEA also triggers tumor cell autophagy and promotes antigen cross-presentation. Autophagosome-enriched fractions of α-TEA-treated tumor cells (α-TAGS) efficiently cross-primed antigen-specific CD8 (+)  T cells and vaccination with dendritic cells (DC) pulsed with α-TAGS reduced lung metastases and increased survival of tumor-bearing mice. Taken together, these observations suggest that both autophagy and apoptosis signaling programs are activated in tumor cells by α-TEA treatment and may contribute to tumor cell death. We propose that autophagy-dependent enhancement of cross-presentation is a novel mechanism of α-TEA-mediated tumor immunity and that α-TEA can be exploited as an adjuvant to enhance the antitumor response.
authors.affiliation: Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hahn
authors.forename: Emmanuel T
authors.initials: ET
authors.lastname: Akporiaye
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D024505:Tocopherols / Q000737:chemistry / Q000494:pharmacology*; D014810:Vitamin E / Q000031:analogs & derivatives
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D014810:Vitamin E; C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid; D024505:Tocopherols