IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion

Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6–activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum–associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti–T cell immunoglobulin mucin-3 (anti–Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti–IL-6 and anti–Tim-3 as an effective marker-guided therapeutic strategy.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
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Source: Yonsei Medical Journal - Category: Universities & Medical Training Authors: Tags: Yonsei Med J Source Type: research
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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Journal of Vascular and Interventional Radiology - Category: Radiology Source Type: research
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Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
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Source: Nature Reviews Gastroenterology and Hepatology - Category: Gastroenterology Authors: Source Type: research
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