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

Youngmin Jeong, Gi Beom Kim, Yuhyun Ji, Gi Jung Kwak, Gi Hoon Nam, Yeonsun Hong, Seohyun Kim, Jinsu An, Sun Hwa Kim, Yoosoo Yang, Hak Suk Chung, In San Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalCancer letters
Volume472
DOIs
Publication statusPublished - 2020 Mar 1

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Dendritic Cells
Escherichia coli
Toll-Like Receptor 4
Neoplasms
Immunotherapy
T-Lymphocytes
monophosphoryl lipid A
Adaptive Immunity
Antigen-Presenting Cells
Melanoma
Therapeutics
Growth

Keywords

  • Antigen presenting cell
  • E.coli-derived monophosphoryl lipid A
  • Immune checkpoint blockade
  • Immuno-adjuvant
  • TLR-4 agonist

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer letters, Vol. 472, 01.03.2020, p. 19-28.

Research output: Contribution to journalArticle

Jeong, Y, Kim, GB, Ji, Y, Kwak, GJ, Nam, GH, Hong, Y, Kim, S, An, J, Kim, SH, Yang, Y, Chung, HS & Kim, IS 2020, 'Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade', Cancer letters, vol. 472, pp. 19-28. https://doi.org/10.1016/j.canlet.2019.12.012
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. / Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade. In: Cancer letters. 2020 ; Vol. 472. pp. 19-28.
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