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

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

doi:10.18632/oncotarget.8098

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.

Highlights

In the past, cancer immunotherapy mainly focused on attacking tumor cells
The combination of a Fibroblast activation protein α (FAP α) vaccine and curcumin stimulated FAP α antibody production and CD8+T cell-mediated killing of FAP α-expressing stromal cells without adverse reactive effects [9]. These results suggest that FAP α, a product preferentially expressed by cancer-associated fibroblasts (CAFs), would be a more effective antigen to target in the setting of cancer immunotherapy
Tumor stromal cells have been suggested as a target for tumor immunotherapy because tumor stromal cells, unlike tumor cells, are diploid, genetically stable, and open to immunological attack

Summary

Introduction

Cancer immunotherapy mainly focused on attacking tumor cells. Cancer immunotherapy is a promising treatment strategy against solid tumors; it cannot completely eradicate them. Given the close interaction between tumor cells and CAFs in the TME, CAF-targeted www.impactjournals.com/oncotarget strategies would be promising for developing integrated cancer immunotherapy [3]. A series of findings about the expression and role of FAP α in pancreatic carcinoma has suggested that FAP α-targeted immunotherapy may be a new treatment for pancreatic cancer patients.

Results

Conclusion