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: Yuhuan Li, Tobias Hahn, Kendra Garrison, Zhi-Hua Cui, Andrew Thorburn, Jacqueline Thorburn, Hong-Ming Hu, Emmanuel T Akporiaye
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 14 Pg. 3535-45 (Jul 15 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22745370 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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