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 1, * , Wan-Ying Xie 2, * , Hong-Sheng Wang 3, * , Jun Du 3 , Bai-Ping Wu 1 , Wei Xu 2 , Hui-Fang Liu 2 , Ping Xiao 1 , Zhi-Gang Liu 4 , Hong-Yan Li 1 , Shuang-Quan Liu 2 , Wen-Jun Yin 2 , Qiu-Gui Zhang 2 , Jian-Ping Liang 5 , Hong-Jun Huang 1 1 Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China 2 Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China 3 Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China 4 Department of Radiation Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China 5 Department 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: hongjunhuanghjh@163.com Jian-Ping Liang, e-mail: liangsugd@vip.sina Qiu-Gui Zhang, e-mail: zhangqg789@163.com 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.