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

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 alpha (FAP alpha) 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 alpha has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a postproline bond. When all FAP alpha-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP alpha antibody, FAP alpha vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP alpha is an adaptive tumor-associated antigen. This review highlights the role of FAP alpha in tumor development, explores the relationship between FAP alpha and immune suppression in the TME, and discusses FAP alpha as a potential immunotherapeutic target.