Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade
- Authors
- Jeong, Youngmin; Kim, Gi Beom; Ji, Yuhyun; Kwak, Gi-Jung; Nam, Gi-Hoon; Hong, Yeonsun; Kim, Seohyun; An, Jinsu; Kim, Sun Hwa; Yang, Yoosoo; Chung, Hak Suk; Kim, 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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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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