The Vitamin E Analogue α-TEA Stimulates Tumor Autophagy and Enhances Antigen Cross-Presentation

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. Cancer Res; 72(14); 3535–45. ©2012 AACR .