In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HIFα express elevated levels of PD-L1. In vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2α, but not of HIF1α, lead to reduced PD-L1 expression. The strong correlation of expression between the HIF2α-specific HIF target Glut1 and PD-L1 confirmed this finding in ccRCC cell lines and tissue. Soluble PD-L1 levels remained constant in the sera of ccRCC patients regardless of the PD-L1 expression status in their tumors. In conclusion, our data suggest PD-L1 as HIF2α target, which is upregulated in pVHL deficient ccRCC. The combination of PD-L1 targeting drugs with HIF inhibiting agents may be an additional option for the treatment of ccRCC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ijc.30077 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Advanced anaplastic thyroid carcinoma with positive expression of PD-L1 response to immune checkpoint inhibitors: A case report.
SAGE Open Med Case Rep
January 2025
Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, China.
Anaplastic thyroid carcinoma (ATC) is one rare type of thyroid carcinoma without standard systemic treatment for advanced disease. Recent evidence has demonstrated promising efficacy of immune checkpoint inhibitors, particularly those targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), in a variety of solid tumors. However, there have been no research of immune checkpoint inhibitors plus chemotherapy in ATC.
View Article and Find Full Text PDFIntroduction: -mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs).
Methods: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance.
Very Early Health Technology Assessment for Potential Predictive Biomarkers in the Treatment of Advanced Non-Small Cell Lung Cancer.
Pharmacoecon Open
January 2025
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Objectives: Immune checkpoint inhibitor (ICI)-containing treatment is currently prescribed as first-line treatment for all patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, only 30-45% of patients show no progression within 12 months after treatment start. Various biomarkers are being studied to save costly and potentially harmful treatment in non-responders.
View Article and Find Full Text PDFThe prevalence of PD-L1 expression in patients with advanced oesophageal cancer: the EXCEED observational study.
J Clin Pathol
January 2025
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Aims: There are limited data on programmed death ligand 1 (PD-L1) expression in oesophageal cancer (OC) from multicentre studies conducted across China. We aimed to determine the prevalence of high PD-L1 expression in patients with advanced OC.
Methods: The EXCEED study was a multicentre, retrospective analysis of data from six tertiary hospitals that evaluated PD-L1 expression in adults with advanced OC or advanced head and neck squamous cell carcinoma.
Modulation of N-glycosylation in the PD-1: PD-L1 axis as a strategy to enhance cancer immunotherapies.
Biochim Biophys Acta Rev Cancer
January 2025
Department of Immunology, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warsaw, Poland. Electronic address:
The modulation of the N-glycosylation status in immune checkpoints, particularly the PD-1/PD-L1 axis, has emerged as a promising approach to enhance cancer immunotherapies. While immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have achieved significant clinical success, recent studies highlight the critical role of N-glycosylation in regulating their expression, stability, and function. Alterations in N-glycosylation might affect the efficacy of ICIs by modulating the interactions between immune checkpoints and antibodies used in therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!