Immunotherapy Targeting Tumor Stromal Fibroblasts Improves Chemotherapy of Breast Cancer

Abstract : We demonstrated that a DNA-based vaccine encoding fibroblast activation protein (FAP), overexpressed on tumor-associated fibroblasts (TAFs), induces a CD8+ T cell response killing TAFs. This effectively suppressed or eradicated primary tumors or their pulmonary metastases in a murine breast carcinoma model. Moreover, eradication of TAFs decreased the interstitial fluid pressure of the tumor since it markedly diminished collagen type I produced by TAFs. This resulted in increased tumor uptake (70%) of doxorubicin which made the combination of the pFAP vaccine with chemotherapy highly effective as it completely eradicated primary breast tumor growth in a mouse tumor model.