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

2016; Impact Journals LLC; Volume: 7; Issue: 22 Linguagem: Inglês

10.18632/oncotarget.8098

1949-2553

Guanmin Jiang, Wei Xu, Jun Du, Kun-Shui Zhang, Qiu-Gui Zhang, Xiaowei Wang, Zhigang Liu, Shuangquan Liu, Wanying Xie, Huifang Liu, Jingshi Liu, WU Bai-ping,

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// Guan-Min Jiang 1,* , Wei Xu 2,* , Jun Du 3 , Kun-Shui Zhang 4 , Qiu-Gui Zhang 2 , Xiao-Wei Wang 1 , Zhi-Gang Liu 5 , Shuang-Quan Liu 2 , Wan-Ying Xie 2 , Hui-Fang Liu 2 , Jing-Shi Liu 6 and Bai-Ping Wu 1 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.