Abstract |
Monophosphoryl lipid A (MPLA) is a toll-like receptor 4 ligand that promotes immune activation in mice and humans, without undesired inflammation. Immunotherapy by the combining immune checkpoint blockade and MPLA has shown promising anti- cancer effects in both mice and humans. In this study, we explored how MPLA enhanced the anti- cancer effects of anti-PD-L1 antibodies (Abs). Anti- cancer immunity induced by the combination of anti-PD-L1 Abs and MPLA failed in CD4 and CD8 cell-depleted mice. Moreover, the combination treatment of anti-PD-L1 Abs and MPLA synergistically enhanced the activation of plasmacytoid dendritic cells (pDCs) in the mouse in vivo, while conventional DCs were not. In addition, mice treated with anti-PD-L1 Abs and MPLA were not protected from B16 melanoma by blockade of interferon-alpha receptor (IFNAR). The combination of anti-PD-L1 Abs and MPLA also promoted human peripheral blood pDC activation and induced IFN-α-dependent T cell activation. Therefore, these results demonstrate that MPLA enhances anti-PD-L1 Ab-mediated anti- cancer immunity through the activation and IFN-α production of pDCs.
|
Authors | Wei Zhang, Seong-Min Lim, Juyoung Hwang, Srinivasan Ramalingam, Myunghee Kim, Jun-O Jin |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 70
Issue 3
Pg. 689-700
(Mar 2021)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 32902663
(Publication Type: Journal Article)
|
Chemical References |
- B7-H1 Antigen
- Biomarkers
- CD274 protein, human
- Cytokines
- Immune Checkpoint Inhibitors
- Lipid A
- monophosphoryl lipid A
|
Topics |
- Animals
- B7-H1 Antigen
(antagonists & inhibitors)
- Biomarkers
- CD8-Positive T-Lymphocytes
(immunology, metabolism)
- Cytokines
(metabolism)
- Dendritic Cells
(drug effects, immunology, metabolism)
- Female
- Humans
- Immune Checkpoint Inhibitors
(pharmacology)
- Immunophenotyping
- Leukocytes, Mononuclear
(immunology, metabolism)
- Lipid A
(analogs & derivatives, pharmacology)
- Lymphocyte Activation
(drug effects, immunology)
- Melanoma, Experimental
- Mice
|