PD-1H/VISTA mediates immune evasion in acute myeloid leukemia
Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics, such as targeted therapy and immunotherapy, including anti-programmed cell death protein (anti-PD) therapy. We demonstrate that programmed death-1 homolog (PD-1H), an immune coinhibitory molecule, is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells express PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell-surface PD-1H by antibody blockade or genetic knockout significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression, and the combination of PD-1H blockade with anti-PD therapy conferred a synergistic antileukemia effect. Our findings provide the basis for PD-1H as a potential therapeutic target for treating human AML.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:134 |
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| Enthalten in: |
The Journal of clinical investigation - 134(2024), 3 vom: 01. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Tae Kon [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer immunotherapy |
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| Anmerkungen: |
Date Completed 09.02.2024 Date Revised 12.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/JCI164325 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365512257 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics, such as targeted therapy and immunotherapy, including anti-programmed cell death protein (anti-PD) therapy. We demonstrate that programmed death-1 homolog (PD-1H), an immune coinhibitory molecule, is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells express PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell-surface PD-1H by antibody blockade or genetic knockout significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression, and the combination of PD-1H blockade with anti-PD therapy conferred a synergistic antileukemia effect. Our findings provide the basis for PD-1H as a potential therapeutic target for treating human AML | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer immunotherapy | |
| 650 | 4 | |a Costimulation | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Leukemias | |
| 650 | 4 | |a Oncology | |
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| 700 | 1 | |a Han, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qianni |e verfasserin |4 aut | |
| 700 | 1 | |a Vandsemb, Esten N |e verfasserin |4 aut | |
| 700 | 1 | |a Fielder, Carly M |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Junshik |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kwang Woon |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, Emily F |e verfasserin |4 aut | |
| 700 | 1 | |a Plowman, R Skipper |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jian-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Badri, Ti |e verfasserin |4 aut | |
| 700 | 1 | |a Sanmamed, Miguel F |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Linghua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tianxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Alawa, Jude |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sang Won |e verfasserin |4 aut | |
| 700 | 1 | |a Zeidan, Amer M |e verfasserin |4 aut | |
| 700 | 1 | |a Halene, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Pillai, Manoj M |e verfasserin |4 aut | |
| 700 | 1 | |a Chandhok, Namrata S |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Mina L |e verfasserin |4 aut | |
| 700 | 1 | |a Gore, Steven D |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lieping |e verfasserin |4 aut | |
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