Cancer-associated fibroblasts (CAFs) constitute a prominent cellular component of the tumor stroma, representing a heterogeneous group of activated fibroblasts. Within the tumor microenvironment (TME), CAFs play various pro-tumorigenic roles, including extracellular matrix remodeling, suppression of anti-tumor immunity, and modulation of tumor cell resistance to therapy. Fibroblast activation protein (FAP), a highly expressed marker on immunosuppressive CAFs, has been identified in several epithelial human cancers such as lung, colon, breast, and prostate cancer. Numerous attempts to target FAP+CAFs for inhibiting tumor progression and enhancing anti-tumor immunity have been reported, however, the translation of FAP-directed therapies into human clinical trials has been unsuccessful. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor therapy that utilizes an antibody-photo-absorbing conjugate activated by near-infrared (NIR) light. In this study, we describe the therapeutic efficacy of anti-FAP near-infrared photoimmunotherapy (NIR-PIT) and subsequent immune activation in two immune-competent murine cancer models. Targeting FAP+ cells effectively suppressed tumor growth and reduced lung metastasis in a spontaneous mouse model of mammary cancer. These findings highlight a promising therapeutic approach for selectively and safely eliminating immunosuppressive FAP+ cells within the tumor microenvironment.
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