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; Hong-Jun Huang

doi:10.18632/oncotarget.4577

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

Oncotarget. 2015 Sep 22;6(28):25932-42. doi: 10.18632/oncotarget.4577.

Authors

Affiliations

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.

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Blotting, Western
Cancer Vaccines / administration & dosage
Cancer Vaccines / immunology
Cell Line, Tumor
Cell Survival / drug effects
Curcumin / administration & dosage
Dose-Response Relationship, Drug
Endopeptidases
Epithelial-Mesenchymal Transition / drug effects*
Female
Gelatinases / antagonists & inhibitors*
Gelatinases / immunology
Gelatinases / metabolism
Immunohistochemistry
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / metabolism
Melanoma, Experimental / pathology
Membrane Proteins / antagonists & inhibitors*
Membrane Proteins / immunology
Membrane Proteins / metabolism
Mice, Inbred C57BL
Oligodeoxyribonucleotides / administration & dosage
Serine Endopeptidases / immunology
Serine Endopeptidases / metabolism
Survival Analysis
Tumor Burden / drug effects
Tumor Necrosis Factor-alpha / metabolism
Tumor Necrosis Factor-alpha / pharmacology

Substances

Cancer Vaccines
CpG ODN 1826
Indoleamine-Pyrrole 2,3,-Dioxygenase
Membrane Proteins
Oligodeoxyribonucleotides
Tumor Necrosis Factor-alpha
Endopeptidases
Serine Endopeptidases
fibroblast activation protein alpha
Gelatinases
Curcumin