Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade.
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Authors
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Jeong, Youngmin1
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Kim, Gi Beom1
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Ji, Yuhyun2
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Kwak, Gi-Jung1
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Nam, Gi-Hoon3
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Hong, Yeonsun1
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Kim, Seohyun1
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An, Jinsu4
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Kim, Sun Hwa3
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Yang, Yoosoo5
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Chung, Hak Suk6
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Kim, In-San7
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1
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
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(North Korea)
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2
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
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(North Korea)
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3
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
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(North Korea)
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4
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
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(North Korea)
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5
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea. Electronic address: [email protected]
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(North Korea)
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6
Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea. Electronic address: [email protected]
,
(North Korea)
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7
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea. Electronic address: [email protected]
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(North Korea)
- Type
- Published Article
- Journal
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Cancer letters
- Publication Date
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Mar 01, 2020
- Volume
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472
- Pages
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19–28
- Identifiers
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DOI: 10.1016/j.canlet.2019.12.012
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PMID: 31857157
- Source
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Medline
- Keywords
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- Language
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English
- License
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Unknown
Abstract
Cancer immunotherapy is a powerful approach for cancer treatment, but its clinical effects rely on the tumor's immune conditions. In particular, low response rates to PD-1 blockades are highly correlated with impaired T cell priming. Here, we demonstrate that E. coli-derived monophosphoryl lipid A (EcML) activates dendritic cells in a toll-like receptor-4 (TLR-4)-dependent manner and increases the sensitivity of cancer cells to anti-PD-1 immunotherapy. EcML is a mixture of 4'-monophosphoryl lipids A (MPLAs) produced directly by an engineered Escherichia coli strain; it has a unique congener composition that differentiates it from the well-established MPLA adjuvants, 3-O-desacyl-4'-monophosphoryl lipid A and glucopyranosyl lipid A. Given that active dendritic cells initiate adaptive immune responses, we investigated the anti-tumor activity of an aqueous formulation of EcML. Upon sensing EcML via TLR-4, dendritic cells matured into powerful antigen-presenting cells that could stimulate naïve T cells. EcML reduced tumor growth in the B16F10 mouse model via dendritic cell activation and potentiated PD-1 blockade therapy in the B16F10-OVA melanoma model. These data identify EcML as a promising TLR-4 agonist that can induce anti-tumor immune responses and potentiate PD-1 blockade therapy against tumors. Copyright © 2019 Elsevier B.V. All rights reserved.
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This record was last updated on 08/13/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/31857157
