Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity

• DOI: 10.1038/s41416-024-02639-1
• Publication Date: 2024-03-30T13:01:49Z
• Authors: Masaaki Akai; Kazuhiro Noma; Takuya Kato; Seitaro Nishimura; Hijiri Matsumoto; Kento Kawasaki; Tomoyoshi Kunitomo; Teruki Kobayashi; Noriyuki Nishiwaki; Hajime Kashima; Satoru Kikuchi; Toshiaki Ohara; Hiroshi Tazawa; Peter L. Choyke; Hisataka Kobayashi; Toshiyoshi Fujiwara
• Keywords: Cancer-Associated Fibroblasts; Immunosuppression; Targeted Therapy; Tumor progression; Tumor-infiltrating lymphocytes

Abstract Background Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a critical role immunosuppression. However, targeted depletion of CAFs is difficult due to their diverse cells origin and resulting lack specific surface markers. Near-infrared photoimmunotherapy (NIR-PIT) novel cancer treatment that leads rapid cell membrane damage. Methods In this study, we used anti-mouse fibroblast activation protein (FAP) antibody target FAP + (FAP-targeted NIR-PIT) investigated whether therapy could suppress progression improve immunity. Results FAP-targeted NIR-PIT induced death without damaging adjacent normal cells. Furthermore, treated mice showed significant regression CAF-rich model accompanied by an increase CD8 infiltrating lymphocytes (TILs). Moreover, tumors increased levels IFN-γ, TNF-α, IL-2 TILs compared with non-treated tumors, suggesting enhanced antitumor Conclusions Cancers FAP-positive TME grow rapidly not only suppresses growth but improves Thus, potential therapeutic strategy for selectively targeting CAF tumors.