Objectives: Recent genomic studies suggest the biological significance of the cylindromatosis (CYLD) gene in thymic epithelial tumors (TETs). CYLD is a crucial regulator of immune response, and we previously reported that CYLD mutation is associated with high PD-L1 expression in thymic carcinoma. Therefore, we wanted to explore the role and mechanism of CYLD in regulating PD-L1 expression in TETs.
Materials And Methods: The role of CYLD in PD-L1 expression was assessed by knockdown of CYLD in TET cells upon stimulation with interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α) or polyinosinic-polycytidylic acid (poly I:C). The molecular mechanism was investigated through analysis of downstream molecules in the STAT1/IRF1 pathway. Moreover, the clinical correlation between low CYLD and high PD-L1 expression, and the clinical impact of CYLD expression were evaluated in tissue microarrays of 105 TET cases.
Results: CYLD knockdown significantly enhanced the expression of PD-L1 in presence of IFN-γ stimulation in most TET cell lines. However, this phenomenon was not observed in presence of TNF-α stimulation. CYLD knockdown upregulated IFN-γ mediated activation of the STAT1/IRF1 axis, which in turn induced PD-L1 expression. Interestingly, we found a significant association between low CYLD expression and ≥ 50 % PD-L1 expression (p = 0.001). In addition, the average proportion of tumor cells exhibiting PD-L1 staining was significantly higher in the low CYLD expression group (24.7 %) than in the high CYLD expression group (5.2 %) (p = 0.005). There was no correlation between CYLD expression and the frequency of pre-existing paraneoplastic auto-immune diseases. In advanced stages (III/IV), the low CYLD expressing group had numerically worse survival than the high CYLD group (log-rank p = 0.089).
Conclusions: Our findings provide insight into the mechanism of regulation of PD-L1 expression by CYLD in TET cells. Tumors with low CYLD expression could be potential targets for PD-1/PD-L1 inhibitors.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.lungcan.2020.07.018 | DOI Listing |
Asian Pac J Cancer Prev
January 2025
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Objective: Programmed Death-Ligand 1 (PD-L1) and Cytotoxic T Lymphocyte -Associated Antigen-4 (CTLA-4) are presently considered as prognostic markers and therapeutic targets in numerous human malignancies. The goal of this study was to determine whether PD-L1 and CTLA-4 might be used to predict patients' survival in Triple Negative Breast Cancer (TNBC).
Methods: This retrospective cohort study analyzed 100 primary TNBC cases that had surgical resection at the Oncology Center of Mansoura University (OCMU), Faculty of Medicine, Egypt.
J Med Chem
January 2025
Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Disease, Ministry of Education; Jiangxi Provincal Key Laboratory of Tissue Engineering; College of Pharmacy, Gannan Medical University, Ganzhou 314000, China.
Histone deacetylase 3 (HDAC3) is a well-established target for cancer therapy. Herein, we developed as a novel HDAC3 inhibitor, which exhibited high HDAC3 inhibitory activity (IC = 42 nM, SI > 161) and displayed potent antiproliferative activity against four cancer cells and further demonstrated excellent antimigratory, anti-invasive, and antiwound healing activities. Further studies revealed that induced a dose-dependent increase in Ac-H3 expression and promoted the degradation of PD-L1.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
Radiation therapy (RT) is a prevalent cancer treatment; however, its therapeutic outcomes are frequently impeded by tumor radioresistance, largely attributed to metabolic reprogramming characterized by increased fatty acid uptake and oxidation. To overcome this limitation, we developed polyphenol-metal coordination polymer (PPWQ), a novel nanoradiotherapy sensitizer specifically designed to regulate fatty acid metabolism and improve RT efficacy. These nanoparticles (NPs) utilize a metal-phenolic network (MPN) to integrate tungsten ions (W), quercetin (QR), and a PD-L1-blocking peptide within a PEG-polyphenol scaffold.
View Article and Find Full Text PDFCancer Imaging
January 2025
Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou District, No. 100, Haining Road, Shanghai, 200080, China.
Background: Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a Ga-labeled anti-PD-L1 nanobody, Ga-NODAGA-NM-01, for PET imaging of PD-L1.
View Article and Find Full Text PDFJ Transl Med
January 2025
School of Nursing, Nanjing Medical University, Nanjing, 211166, China.
Background: Tumor-associated fibrosis modifies the tumor microenvironment (TME), hinders the infiltration and activity of cytotoxic immune cells, and is a critical pathological process leading to the ineffectiveness of tumor immunotherapy in gastric cancer (GC). However, the specific mechanisms and interventions are yet to be fully explored.
Methods: Our study included 375 gastric cancer samples from TCGA, 1 single-cell RNA sequencing (scRNA-seq) dataset comprising of 15 gastric cancer samples from GEO, 19 cohorts of immunotherapy and 2 GWAS datasets.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!