期刊
ONCOTARGET
卷 6, 期 28, 页码 25932-25942出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4577
关键词
curcumin; indolamine-2,3-dioxygenase; immunotherapy; melanoma; fibroblast activation protein-alpha
资金
- Hunan Natural Science Foundation [13JJ4078]
- Bureau of Hunan Provincial Science and Technology [2013sk5010, 2012sk2007, 2012sk3252]
- National Program on Key Basic Research Project (973 Program) [2011CB935800]
- National Natural Science Foundation of China [81472470, 81302317, 31101071]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2014A030306025]
- Fundamental Research Funds for the Central Universities (Sun Yat-sen University) [12ykpy09]
- Science and Technology Planning Project of Guangdong Province, China [2012B031500005]
Fibroblast activation protein alpha (FAP alpha) is a potential target for cancer therapy. However, elimination of FAP alpha+ fibroblasts activates secretion of IFN-gamma and TNF-alpha. IFN-gamma can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-alpha can induce EMT. These two reactive effects would limit the efficacy of a tumor vaccine. We found that curcumin can inhibit IDO expression and TNF-alpha-induced EMT. Moreover, FAP alpha c vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAP alpha c vaccine, CpG and curcumin stimulated FAP alpha antibody production and CD8+ T cell-mediated killing of FAP alpha-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAP alpha c vaccine for melanoma therapy.
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