1. Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity.
- Author
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Akai M, Noma K, Kato T, Nishimura S, Matsumoto H, Kawasaki K, Kunitomo T, Kobayashi T, Nishiwaki N, Kashima H, Kikuchi S, Ohara T, Tazawa H, Choyke PL, Kobayashi H, and Fujiwara T
- Subjects
- Animals, Humans, Mice, CD8-Positive T-Lymphocytes immunology, Cell Line, Tumor, Endopeptidases, Gelatinases metabolism, Infrared Rays therapeutic use, Lymphocytes, Tumor-Infiltrating immunology, Membrane Proteins metabolism, Mice, Inbred C57BL, Phototherapy methods, Serine Endopeptidases metabolism, Cancer-Associated Fibroblasts immunology, Cancer-Associated Fibroblasts metabolism, Immunotherapy methods, Tumor Microenvironment immunology
- Abstract
Background: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a critical role in tumor immunosuppression. However, targeted depletion of CAFs is difficult due to their diverse cells of origin and the resulting lack of specific surface markers. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that leads to rapid cell membrane damage., Methods: In this study, we used anti-mouse fibroblast activation protein (FAP) antibody to target FAP
+ CAFs (FAP-targeted NIR-PIT) and investigated whether this therapy could suppress tumor progression and improve tumor immunity., Results: FAP-targeted NIR-PIT induced specific cell death in CAFs without damaging adjacent normal cells. Furthermore, FAP-targeted NIR-PIT treated mice showed significant tumor regression in the CAF-rich tumor model accompanied by an increase in CD8+ tumor infiltrating lymphocytes (TILs). Moreover, treated tumors showed increased levels of IFN-γ, TNF-α, and IL-2 in CD8+ TILs compared with non-treated tumors, suggesting enhanced antitumor immunity., Conclusions: Cancers with FAP-positive CAFs in their TME grow rapidly and FAP-targeted NIR-PIT not only suppresses their growth but improves tumor immunosuppression. Thus, FAP-targeted NIR-PIT is a potential therapeutic strategy for selectively targeting the TME of CAF+ tumors., (© 2024. The Author(s).)- Published
- 2024
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