Fibroblast activation proteins-α suppress tumor immunity by regulating T cells and tumor-associated macrophages

Fibroblast activation protein-alpha (FAP alpha) is a type-II cell-surface-bound integral transmembrane serine protease and selectively overexpressed by tumor-associated stromal fibroblasts (TAFs), which are the main components in the tumor microenvironment, in > 90% of malignant epithelial carcinomas. FAPa regulates the immunosuppression of tumor cells in the tumor microenvironment. Regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are the major immunosuppressive cells in the tumor microenvironment. However, the effect of FAP alpha on Tregs and TAMs is unknown. The non-enzymatic function of FAP alpha on Treg and TAM was investigated. In this study, we confirm that FAP alpha can promote the generation of Tregs and TAMs, which suggests that FAP alpha plays a immunosuppressive role in the tumor microenvironment and provides evidence for FAP alpha as a potent immunotherapeutic target for cancer.