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

Authors
Jeong, YoungminKim, Gi BeomJi, YuhyunKwak, Gi-JungNam, Gi-HoonHong, YeonsunKim, SeohyunAn, JinsuKim, Sun HwaYang, YoosooChung, Hak SukKim, In-San
Issue Date
2020
Publisher
ELSEVIER IRELAND LTD
Keywords
TLR-4 agonist; Antigen presenting cell; E.coli-derived monophosphoryl lipid A; Immuno-adjuvant; Immune checkpoint blockade
Citation
CANCER LETTERS, v.472, pp.19 - 28
Indexed
SCIE
SCOPUS
Journal Title
CANCER LETTERS
Volume
472
Start Page
19
End Page
28
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/59047
DOI
10.1016/j.canlet.2019.12.012
ISSN
0304-3835
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 naive 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.
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Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles

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