Oncotarget

Research Papers:

Curcumin combined with FAPαc vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma

Guan-Min Jiang, Wan-Ying Xie, Hong-Sheng Wang, Jun Du, Bai-Ping Wu, Wei Xu, Hui-Fang Liu, Ping Xiao, Zhi-Gang Liu, Hong-Yan Li, Shuang-Quan Liu, Wen-Jun Yin, Qiu-Gui Zhang, Jian-Ping Liang and Hong-Jun Huang _

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Oncotarget. 2015; 6:25932-25942. https://doi.org/10.18632/oncotarget.4577

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Abstract

Guan-Min Jiang1,*, Wan-Ying Xie2,*, Hong-Sheng Wang3,*, Jun Du3, Bai-Ping Wu1, Wei Xu2, Hui-Fang Liu2, Ping Xiao1, Zhi-Gang Liu4, Hong-Yan Li1, Shuang-Quan Liu2, Wen-Jun Yin2, Qiu-Gui Zhang2, Jian-Ping Liang5, Hong-Jun Huang1

1Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China

2Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China

3Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China

4Department of Radiation Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China

5Department of Thoracic Surgery 2, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China

*These authors have contributed equally to this work

Correspondence to:

Hong-Jun Huang, e-mail: [email protected]

Jian-Ping Liang, e-mail: [email protected]

Qiu-Gui Zhang, e-mail: [email protected]

Keywords: curcumin, indolamine-2,3-dioxygenase, immunotherapy, melanoma, fibroblast activation protein α

Received: April 07, 2015     Accepted: July 08, 2015     Published: July 20, 2015

ABSTRACT

Fibroblast activation protein α (FAPα) is a potential target for cancer therapy. However, elimination of FAPα+ fibroblasts activates secretion of IFN-γ and TNF-α. IFN-γ can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-α 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-α-induced EMT. Moreover, FAPαc vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAPαc vaccine, CpG and curcumin stimulated FAPα antibody production and CD8+ T cell-mediated killing of FAPα-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAPαc vaccine for melanoma therapy.


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