Microenvironmental IL-6 inhibits anti-cancer immune responses
WEBOct 28, 2021 · We also show that IL-6 suppresses the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. Our results suggest that IL-6 is a key regulator of anti-cancer immune...
IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to …
WEBJul 15, 2019 · 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.
Mechanisms regulating PD-L1 expression in cancers and ... - Nature
WEBFeb 7, 2022 · Antagonistic antibodies targeting the inhibitory immune-checkpoint receptor PD-1 or its ligand PD-L1 are used to treat a wide range of cancer types and can substantially improve patient...
CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 ...
WEBJan 17, 2023 · In pre-clinical models, combined blockade of PD-L1 and the IL-6 receptor (IL6R) causes synergistic regression of large established tumors and substantially improves anti-tumor CD8 + cytotoxic T lymphocyte (CTL) responses compared with anti-PD-L1 alone.
IL-6 promotes PD-L1 expression in monocytes and macrophages by ... - PubMed
WEBIncreased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25-3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.
IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to …
WEBJul 7, 2019 · In this study, we identified JAK1 as a PD-L1–binding partner in the ER and showed that Tyr phosphorylation on PD-L1 by the IL-6/JAK1 pathway is essential for PD-L1’s association with the N-glycosyltransferase STT3A to prevent of ubiquitination and degradation of PD-L1.
IL-6 promotes PD-L1 expression in monocytes and macrophages …
WEBJun 24, 2020 · IL-6 treatment significantly increased Pd-L1/PD-L1 expression both directly and in an INF-γ–dependent manner in WT and normal-PTPRO–expressing macrophages 72 hours after the treatment. The IL-6 promotion was particularly evident for IFN-γ–induced Pd-1/PD-L1 expression in Ptpro KO and PTPRO knockdown macrophages (figure …
Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates …
WEBSep 4, 2018 · We found that PD-1/PD-L1 blockade prompted PD-1 + macrophages to produce IL6 in the tumor microenvironment. Depletion of macrophages in melanoma-bearing mice reduced the levels of IL6 during PD-L1 blockade, suggesting macrophages are responsible for the IL6-mediated defective CD4 + Th1 response.
IL-6 influences PD-L1 expression in monocytes and macrophages …
WEBMay 25, 2020 · A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25-3p axis.
Systematic analysis of IL-6 as a predictive biomarker and …
WEBMay 13, 2022 · Results in vitro showed that PD-L1 expression in the tumor was enhanced by IL-6 via the JAK1/Stat3 pathway, which induced immune evasion. Notably, an adverse correlation was found between IL-6 levels and CD8 + T cells.
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