The application of the fibroblast activation protein α-targeted immunotherapy strategy
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Guan-Min Jiang1,*, Wei Xu2,*, Jun Du3, Kun-Shui Zhang4, Qiu-Gui Zhang2, Xiao-Wei Wang1, Zhi-Gang Liu5, Shuang-Quan Liu2, Wan-Ying Xie2, Hui-Fang Liu2, Jing-Shi Liu6 and Bai-Ping Wu1
1 Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
2 Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China
3 Department of Microbial and Biochemical Pharmacy School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
4 Department of Pharmacy, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
5 Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
6 Department of Anesthesia, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
* These authors have contributed equally to this work
Guan-Min Jiang, email:
Bai-Ping Wu, email:
Jing-Shi Liu, email:
Keywords: fibroblast activation protein α, tumor microenvironment, immune suppression, immunotherapy
Received: December 04, 2015 Accepted: February 28, 2016 Published: March 15, 2016
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.
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