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 alphatocopheryloxyacetic acid (α-TEA), an esterase-resistant, semi-synthetic derivative of vitamin E (R-R-R-a-tocopherol). New information now shows that a-TEA also triggers tumor cell autophagy and promotes antigen cross-presentation. Autophagosome-enriched fractions of a-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. © 2013 Landes Bioscience.