The vitamin E analogue α-TEA stimulates tumor autophagy and enhances antigen cross-presentation

Cancer Res. 2012 Jul 15;72(14):3535-45. doi: 10.1158/0008-5472.CAN-11-3103. Epub 2012 Jun 28.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adenocarcinoma of Lung
  • Animals
  • Antigen Presentation / drug effects*
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cell Survival
  • Cross-Priming / drug effects*
  • Dendritic Cells / immunology
  • Female
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lymphocyte Activation
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Tocopherols / pharmacology*
  • Vaccination


  • 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid
  • Tocopherols