Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade
- Dendritic cell activation by an E. coli-derived monophosphoryl lipid A enhances the efficacy of PD-1 blockade
- 김선화; 정학숙; 김인산; 양유수; 남기훈; 홍연선; 지유현; 정영민; 곽기정; 김기범; 김서현; 안진수
- Issue Date
- Cancer letters
- VOL 472-28
- 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 naï ve 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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