Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy
Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy. We identified paclitaxel as a universal adjuvant that efficiently potentiated ADCP by a variety of anticancer antibodies in multiple cancers. Rather than eliciting cytotoxicity on cancer cells, paclitaxel polarized macrophages toward a state with enhanced phagocytic ability. Paclitaxel-treated macrophages down-regulated cell surface CSF1R whose expression was negatively correlated with patient survival in multiple malignancies. The suppression of CSF1R in macrophages enhanced ADCP of cancer cells, suggesting a role of CSF1R in regulating macrophage phagocytic ability. Together, these findings define a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and promote the therapeutic efficacy of clinical anticancer antibodies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Science advances - 8(2022), 11 vom: 18. März, Seite eabl9171 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Xu [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 04.04.2022 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.abl9171 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM338334238 |
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| 520 | |a Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy. We identified paclitaxel as a universal adjuvant that efficiently potentiated ADCP by a variety of anticancer antibodies in multiple cancers. Rather than eliciting cytotoxicity on cancer cells, paclitaxel polarized macrophages toward a state with enhanced phagocytic ability. Paclitaxel-treated macrophages down-regulated cell surface CSF1R whose expression was negatively correlated with patient survival in multiple malignancies. The suppression of CSF1R in macrophages enhanced ADCP of cancer cells, suggesting a role of CSF1R in regulating macrophage phagocytic ability. Together, these findings define a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and promote the therapeutic efficacy of clinical anticancer antibodies | ||
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| 700 | 1 | |a Chen, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bolei |e verfasserin |4 aut | |
| 700 | 1 | |a Dang, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wencan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Xiancai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chongkai |e verfasserin |4 aut | |
| 700 | 1 | |a Raoof, Mustafa |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Zuoming |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Fakih, Marwan G |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Mingye |e verfasserin |4 aut | |
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