In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 14 ( 2012-07-15), p. 3535-3545
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. Cancer Res; 72(14); 3535–45. ©2012 AACR.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-11-3103
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
