title: Curcumin combined with FAPαc vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma.
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.
authors: Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Guan-Min
authors: GM
authors: Jiang
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Wan-Ying
authors: WY
authors: Xie
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
authors: Hong-Sheng
authors: HS
authors: Wang
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
authors: Jun
authors: J
authors: Du
authors: Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Bai-Ping
authors: BP
authors: Wu
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Wei
authors: W
authors: Xu
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Hui-Fang
authors: HF
authors: Liu
authors: Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Ping
authors: P
authors: Xiao
authors: Department of Radiation Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Zhi-Gang
authors: ZG
authors: Liu
authors: Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Hong-Yan
authors: HY
authors: Li
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Shuang-Quan
authors: SQ
authors: Liu
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Wen-Jun
authors: WJ
authors: Yin
authors: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, 421001, PR China.
authors: Qiu-Gui
authors: QG
authors: Zhang
authors: Department of Thoracic Surgery 2, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Jian-Ping
authors: JP
authors: Liang
authors: Department of Clinical Laboratory, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, PR China.
authors: Hong-Jun
authors: HJ
authors: Huang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D019496:Cancer Vaccines; D003474:Curcumin; D010450:Endopeptidases; D018093:Gelatinases; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D012697:Serine Endopeptidases; D014409:Tumor Necrosis Factor-alpha; D000099167:Fibroblast Activation Protein Alpha; C423449:CpG ODN 1826
keywords: curcumin; fibroblast activation protein α; immunotherapy; indolamine-2,3-dioxygenase; melanoma