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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Li Y,Hahn T,Garrison K,Cui ZH,Thorburn A,Thorburn J,Hu HM,Akporiaye ETdoi
10.1158/0008-5472.CAN-11-3103subject
Has Abstractpub_date
2012-07-15 00:00:00pages
3535-45issue
14eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-3103journal_volume
72pub_type
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