title: The vitamin E analogue α-TEA stimulates tumor autophagy and enhances antigen cross-presentation.
abstract: The semisynthetic vitamin E derivative alpha-tocopheryloxyacetic acid (α-TEA) induces tumor cell apoptosis and may offer a simple adjuvant supplement for cancer therapy if its mechanisms can be better understood. Here we report that α-TEA also triggers tumor cell autophagy and that it improves cross-presentation of tumor antigens to the immune system. α-TEA stimulated both apoptosis and autophagy in murine mammary and lung cancer cells and inhibition of caspase-dependent apoptosis enhanced α-TEA-induced autophagy. Cell exposure to α-TEA generated double-membrane-bound vesicles indicative of autophagosomes, which efficiently cross-primed antigen-specific CD8(+) T cells. Notably, vaccination with dendritic cells pulsed with α-TEA-generated autophagosomes reduced lung metastases and increased the survival of tumor-bearing mice. Taken together, our findings suggest that both autophagy and apoptosis signaling programs are activated during α-TEA-induced tumor cell killing. We suggest that the ability of α-TEA to stimulate autophagy and enhance cross-priming of CD8(+) T cells might be exploited as an adjuvant strategy to improve stimulation of antitumor immune responses.
authors: Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon 97213, USA.
authors: Yuhuan
authors: Y
authors: Li
authors: Tobias
authors: T
authors: Hahn
authors: Kendra
authors: K
authors: Garrison
authors: Zhi-Hua
authors: ZH
authors: Cui
authors: Andrew
authors: A
authors: Thorburn
authors: Jacqueline
authors: J
authors: Thorburn
authors: Hong-Ming
authors: HM
authors: Hu
authors: Emmanuel T
authors: ET
authors: Akporiaye
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival; D045142:Cross-Priming / Q000187:drug effects*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D024505:Tocopherols / Q000494:pharmacology*; D014611:Vaccination
chemical_list: C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid; D024505:Tocopherols