Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model

Unlike heterogeneous tumor cells, cancer-associated fibroblasts (CAF) are genetically more stable which serve as a reliable target for tumor immunotherapy. Fibroblast activation protein (FAP) which is restrictively expressed in tumor cells and CAF in vivo and plays a prominent role in tumor initiation, progression, and metastasis can function as a tumor rejection antigen. In the current study, we have constructed artificial FAP+ stromal cells which mimicked the FAP+ CAF in vivo. We immunized a breast cancer mouse model with FAP+ stromal cells to perform immunotherapy against FAP+ cells in the tumor microenvironment. By forced expression of FAP, we have obtained FAP+ stromal cells whose phenotype was CD11b+/CD34+/Sca-1+/FSP-1+/MHC class I+. Interestingly, proliferation capacity of the fibroblasts was significantly enhanced by FAP. In the breast cancer-bearing mouse model, vaccination with FAP+ stromal cells has significantly inhibited the growth of allograft tumor and reduced lung metastasis indeed. Depletion of T cell assays has suggested that both CD4+ and CD8+ T cells were involved in the tumor cytotoxic immune response. Furthermore, tumor tissue from FAP-immunized mice revealed that targeting FAP+ CAF has induced apoptosis and decreased collagen type I and CD31 expression in the tumor microenvironment. These results implicated that immunization with FAP+ stromal cells led to the disruption of the tumor microenvironment. Our study may provide a novel strategy for immunotherapy of a broad range of cancer.