Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (-) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.
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http://dx.doi.org/10.1038/s41598-021-81667-w | DOI Listing |
J Adv Res
December 2024
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150040, China; Lead Contact. Electronic address:
Introduction: Altered epigenetic reprogramming enables breast cancer cells to adapt to hypoxic stress. Hypoxic microenvironment can alter immune cell infiltration and function, limiting the effectiveness of immunotherapy.
Objectives: The study aimed to identify how fat mass and obesity-associated protein (FTO) helps breast cancer cells cope with the hypoxic microenvironment and the mechanisms behind breast cancer cell resistance to tumor immunity.
Cancer Res Commun
December 2024
Henry Ford Health System, Detroit, Michigan, United States.
Pancreatic cancer is the third leading cause of cancer-related death in the US. Black or African American patients have a higher incidence of pancreatic cancer compared to other racial groups. It is unclear whether distinct molecular mechanisms are involved in the development of pancreatic cancer in different racial groups.
View Article and Find Full Text PDFWorld J Oncol
December 2024
Department of Otolaryngology-Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
Background: The effectiveness of immune checkpoint therapy highlights the need to understand abnormal programmed cell death protein-1 (PD-1) expression in nasopharyngeal carcinoma (NPC), especially when treatments fail, or resistance develops. Interferon gamma (IFN-γ) signaling is crucial for regulating programmed cell death-ligand 1 (PD-L1) expression. Our study focuses on interferon gamma receptor 2 (IFNGR2), an essential part of the IFN-γ pathway, and its impact on malignant traits in NPC.
View Article and Find Full Text PDFJ Formos Med Assoc
December 2024
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Background: PD-L1 is associated with poor efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in untreated EGFR-mutant non-small-cell lung cancer (NSCLC). Whether PD-L1 is also predictive of osimertinib efficacy in pre-treated patients with an acquired EGFR T790 M mutation is unclear.
Patients And Methods: PD-L1 expression and tumor microenvironments were evaluated in tumors from EGFR-mutant T790 M + NSCLC patients treated with osimertinib.
Discov Oncol
December 2024
Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Purpose: Ovarian cancer (OV) remains the most lethal gynecological malignancy, underscoring the critical need for robust prognostic biomarkers to enhance patient outcomes. In this study, we classified OV patients by their interferon-stimulated gene (ISG) expression profiles and investigated the associations between these subtypes, the immune microenvironment, and survival outcomes.
Methods: We employed consensus clustering in the TCGA-OV cohort (n = 376) to classify patients into ISG-related subgroups.
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