Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
British journal of cancer - (2024) vom: 30. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Akai, Masaaki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 30.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1038/s41416-024-02639-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370448324 |
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| 100 | 1 | |a Akai, Masaaki |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Noma, Kazuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Nishimura, Seitaro |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumoto, Hijiri |e verfasserin |4 aut | |
| 700 | 1 | |a Kawasaki, Kento |e verfasserin |4 aut | |
| 700 | 1 | |a Kunitomo, Tomoyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Teruki |e verfasserin |4 aut | |
| 700 | 1 | |a Nishiwaki, Noriyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kashima, Hajime |e verfasserin |4 aut | |
| 700 | 1 | |a Kikuchi, Satoru |e verfasserin |4 aut | |
| 700 | 1 | |a Ohara, Toshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Tazawa, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Choyke, Peter L |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Hisataka |e verfasserin |4 aut | |
| 700 | 1 | |a Fujiwara, Toshiyoshi |e verfasserin |4 aut | |
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