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.
The objective of this study was to evaluate the anticancer activity on cancer cell models of a drug delivery system consisting of poly (l-lactic) acid/Pluronic® F-127 (PLLA/PF127) loaded with the new N-butylpyridoquinoxaline 1,4-dioxide (NBPQD) or 2-amino-3-cyano-6-methylquinoxaline 1,4-dioxide (ACMQD) that was synthesized using an electrospinning process compared to free NBPQD and ACMQD. PLLA/PF127-NBPQD and PLLA/PF127-ACMQD nanofibers were prepared, and their shape, size, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA) analysis, water contact angel (WCA), drug release, anticancer activity agai...
CONCLUSION: LINC00665 was involved in cell viability, apoptosis, and autophagy in HCC via miR-186-5p/MAP4K3 axis, which may provide a new approach for HCC treatment. PMID: 31433582 [PubMed - in process]
CONCLUSIONS This study was the first to demonstrate that SUCO was overexpressed in HCC-tissues, and that high expression of SUCO was significantly related to poor overall survival in HCC patients. SUCO might be a potential diagnostic biomarker for HCC patients, which promotes the tumorigenesis and progression of HCC. PMID: 31434866 [PubMed - in process]
Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh‑7 cells by regulating the ERK‑VEGF/MMP9 signaling pathway. Mol Med Rep. 2019 Aug 06;: Authors: Chen Y, Chen X, Ding X, Wang Y Abstract Transcatheter arterial embolization (TAE) therapy has been used in the treatment of inoperable hepatocellular carcinoma (HCC). However, tumor recurrence and metastasis are common in patients after TAE, and these processes may be caused by circulating tumor cells (CTCs). Epithelial‑mesenchymal transition (EMT) serves important roles in CTCs, and abnormal expression and activation of epidermal growt...
ConclusionsThese results verified the molecular mechanism of ERJR that has been used in traditional anti-cancer remedy and suggest that it can be developed as a promising therapy for cancer metastasis in the future.Graphical abstract
Publication date: September 2019Source: Journal of Vascular and Interventional Radiology, Volume 30, Issue 9Author(s): Lili Zheng, Fubo Zhou, Xiaoling Yu, Ping Liang, Zhigang Cheng, Zhiyu Han, Jie Yu, Fangyi Liu, Weiping WangAbstractPurposeTo identify risk factors for hypertensive crisis (HC) during ultrasound-guided percutaneous microwave (MW) ablation of adrenal neoplasms.Materials and MethodsPatients who underwent MW ablation for adrenal tumors between April 2006 and November 2017 were retrospectively identified for this study (51 consecutive patients; 35 males, 16 females; mean age, 55 years; range, 15–85 years)....
CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR. PMID: 31427562 [PubMed - in process]
Conclusions: These findings suggest that YLE is sufficient for application as a promising anti-liver drug in herbal medicine.
Nature Reviews Gastroenterology &Hepatology, Published online: 22 August 2019; doi:10.1038/s41575-019-0186-yHepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. This Review summarizes the epidemiology, risk factors (including viral hepatitis and NAFLD), molecular profiles and treatment of HCC, providing insights into how the global burden of HCC can be reduced.
ConclusionOncogenic BCL9 proteins represent promising targets for cancer therapy and inhibiting them may be particularly beneficial in Wnt-inactive HCCs.Graphic abstract