Publications

BibTex format

@article{Pinato:2017:10.1080/2162402X.2017.1358332,
author = {Pinato, DJ and Black, J and Trousil, S and Dina, R and Trivedi, P and Mauri, F and Sharma, R},
doi = {10.1080/2162402X.2017.1358332},
journal = {OncoImmunology},
title = {Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: relationship with the hypoxic response, immune evasion and malignant behaviour.},
url = {http://dx.doi.org/10.1080/2162402X.2017.1358332},
volume = {6},
year = {2017}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: The hypoxic response underlies the pathogenesis and malignant behaviour of PCC/PGL. Regulation of PD-1 receptor-ligand signalling, a therapeutically actionable driver of the anti-tumour 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. Methods: Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 & 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). Results: In total, 100 patients, 10% malignant, 64% PCC, 29% familial with a median tumour size of 4.7 cm (range 1-14) were included. Median follow-up was 4.7 years. 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 behaviour (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.Conclusions: 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 tumours.
AU  - Pinato,DJ
AU  - Black,J
AU  - Trousil,S
AU  - Dina,R
AU  - Trivedi,P
AU  - Mauri,F
AU  - Sharma,R
DO  - 10.1080/2162402X.2017.1358332
PY  - 2017///
SN  - 2162-4011
TI  - Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: relationship with the hypoxic response, immune evasion and malignant behaviour.
T2  - OncoImmunology
UR  - http://dx.doi.org/10.1080/2162402X.2017.1358332
UR  - http://hdl.handle.net/10044/1/50128
VL  - 6
ER  -

Download

ProfessorRohiniSharma

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)