ArticleOncoimmunology
Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: Relationship with the hypoxic response, immune evasion and malignant behavior.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
- Phase 2 study of pembrolizumab in patients with advanced rare cancers.Journal for immunotherapy of cancer · 2020Trial
- Integrated hypoxia and metabolic gene signature to predict clinical outcomes and therapeutic vulnerabilities in lung adenocarcinoma.Journal of thoracic disease · 2026Article
- Multi-omics insights into metastatic pheochromocytomas and paragangliomas: Mechanisms, signatures, and prediction models.Hormones (Athens, Greece) · 2026Review
- Unveiling the prognostic and therapeutic landscape of the zinc transporter protein SLC39A family in colorectal cancer through multi-omics and machine learning approaches.Clinical and experimental medicine · 2026Article
- Transient intracellular expression of PD-L1 and VEGFR2 bispecific nanobody in cancer cells inspires long-term T cell activation and infiltration to combat tumor and inhibit cancer metastasis.Molecular cancer · 2025Article
- Clinicopathological data and the role of miRNA expression in patients with pheochromocytomas/paragangliomas.Frontiers in endocrinology · 2025Article
- Treatment of metastatic bladder paraganglioma with cadonilimab plus radiotherapy: a case report and literature review.Frontiers in medicine · 2025Article
- The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.Endocrine reviews · 2024Review
- Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma.Cancers · 2024Article
- The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Alleviating hypoxia to improve cancer immunotherapy.Oncogene · 2023Review
- Article
- Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Mechanisms of HIF-driven immunosuppression in tumour microenvironment.Journal of the Egyptian National Cancer Institute · 2023Review
- Tumour microenvironment in pheochromocytoma and paraganglioma.Frontiers in endocrinology · 2023Review
- Pseudohypoxia in paraganglioma and pheochromocytoma is associated with an immunosuppressive phenotype.The Journal of pathology · 2023Article
- Immune Profiling of Meningiomas.Advances in experimental medicine and biology · 2023Review
- Transcriptome-guided resolution of tumor microenvironment interactions in pheochromocytoma and paraganglioma subtypes.Journal of endocrinological investigation · 2022Article
- Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A). We explored the biologic significance of PD ligands expression using gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) for PCC/PGL (n = 184). In total, 100 patients, 10% malignant, 64% PCC, 29% familial with median tumor size of 4.7 cm (range 1-14) were included. Median follow-up was 4.7 y. We found PD-L1 expression in 18% of PCC/PGL, which was independent of adverse pathological features including capsular (CI), vascular invasion (VI), necrosis (N) and expression of biomarkers of hypoxia. PD-L2 expression (16%) strongly correlated with CI, VI, N and malignant behavior (p < 0.05) and was associated with stronger Hif-1a and CaIX immunolabeling (p < 0.01). PD-L2 was predictive of shorter survival (162 versus 309 months, HR 3.1 95%CI 1.1-9.2, p = 0.02). GSEA on TGCA samples confirmed enrichment of transcripts involved in hypoxia and anti-cancer immunity. We report for the first time PD ligands expression in PCC/PGL with a distinctive prognostic, clinico-pathologic and immuno-biologic role. These findings support a potential therapeutic role for PD-1/PD-L1 targeted checkpoint inhibitors in these tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.