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

ABSTRACT: The semisynthetic vitamin E derivative alpha-tocopheryloxyacetic acid (?-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 ?-TEA also triggers tumor cell autophagy and that it improves cross-presentation of tumor antigens to the immune system. ?-TEA stimulated both apoptosis and autophagy in murine mammary and lung cancer cells and inhibition of caspase-dependent apoptosis enhanced ?-TEA-induced autophagy. Cell exposure to ?-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 ?-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 ?-TEA-induced tumor cell killing. We suggest that the ability of ?-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.

SUBMITTER: Li Y 

PROVIDER: S-EPMC3576035 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature