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Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade.

Authors
  • Jeong, Youngmin1
  • Kim, Gi Beom1
  • Ji, Yuhyun2
  • Kwak, Gi-Jung1
  • Nam, Gi-Hoon3
  • Hong, Yeonsun1
  • Kim, Seohyun1
  • An, Jinsu4
  • Kim, Sun Hwa3
  • Yang, Yoosoo5
  • Chung, Hak Suk6
  • Kim, In-San7
  • 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. , (North Korea)
  • 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. , (North Korea)
  • 3 Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea. , (North Korea)
  • 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. , (North Korea)
  • 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] , (North Korea)
  • 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)
  • 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] , (North Korea)
Type
Published Article
Journal
Cancer letters
Publication Date
Mar 01, 2020
Volume
472
Pages
19–28
Identifiers
DOI: 10.1016/j.canlet.2019.12.012
PMID: 31857157
Source
Medline
Keywords
Language
English
License
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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