Oncotarget

Reviews:

The application of the fibroblast activation protein α-targeted immunotherapy strategy

Guan-Min Jiang, Wei Xu, Jun Du, Kun-Shui Zhang, Qiu-Gui Zhang, Xiao-Wei Wang, Zhi-Gang Liu, Shuang-Quan Liu, Wan-Ying Xie, Hui-Fang Liu, Jing-Shi Liu and Bai-Ping Wu _

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Oncotarget. 2016; 7:33472-33482. https://doi.org/10.18632/oncotarget.8098

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Abstract

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

Correspondence to:

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

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.


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