title: The application of the fibroblast activation protein α-targeted immunotherapy strategy.
abstract: Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target.
authors.affiliation: Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Guan-Min
authors.initials: GM
authors.lastname: Jiang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Microbial and Biochemical Pharmacy School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Kun-Shui
authors.initials: KS
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
authors.forename: Qiu-Gui
authors.initials: QG
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
authors.forename: Shuang-Quan
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Liu
authors.affiliation: Department of Anesthesia, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Bai-Ping
authors.initials: BP
authors.lastname: Wu
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D010450:Endopeptidases; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019139:Tumor Escape; D059016:Tumor Microenvironment; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000074322:Antineoplastic Agents, Immunological; D019496:Cancer Vaccines; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: fibroblast activation protein α; immune suppression; immunotherapy; tumor microenvironment