PD-L1 expression correlates with VEGF and microvessel density in patients with uniformly treated classical Hodgkin lymphoma

• Published in: Annals of hematology 2017-11, Vol.96 (11), p.1883-1890
• Main Authors: Koh, Young Wha, Han, Jae-Ho, Yoon, Dok Hyun, Suh, Cheolwon, Huh, Jooryung
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; B7-H1 Antigen - biosynthesis; B7-H1 Antigen - genetics; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Hematology; Hodgkin Disease - drug therapy; Hodgkin Disease - genetics; Hodgkin Disease - metabolism; Humans; Lymphoma; Male; Medical prognosis; Medicine; Medicine & Public Health; Microvessels - drug effects; Microvessels - metabolism; Middle Aged; Multivariate analysis; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Oncology; Original Article; Retrospective Studies; Treatment Outcome; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Young Adult
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-017-3115-6

Recent studies have reported the associations between programmed death-ligand 1 (PD-L1) or PD-L2/PD-1 pathways and pro-angiogenic genes including hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) in several malignancies. However, no study has examined the relationship or prognostic implication of PD-L1, PD-L2, PD-1, VEGF expression, and microvessel density (MVD) in classical Hodgkin lymphoma (cHL) patients. Diagnostic tissues from 109 patients with doxorubicin, bleomycin, vinblastine, and dacarbazine-treated cHL were evaluated retrospectively by immunohistochemical analysis for PD-L1, PD-L2, PD-1, VEGF expression, and for CD31 expression as a measure of MVD. There was a positive correlation between PD-L1 and VEGF expression ( P  = 0.008) and additionally between PD-L2 and VEGF expression ( P  = 0.001). The mean MVD in tumors positive for both PD-L1 and VEGF was significantly ( P  = 0.022) higher than the mean MVD in tumors negative for both markers. High PD-1 expression group had lower ( P  = 0.019) 5-year overall survival rate than low PD-1 expression group. Multivariate analysis revealed that PD-1 was an independent prognostic factor for cHL with significance ( P  = 0.026). However, PD-L1, PD-L2, and VEGF expression had no prognostic impact. Our data confirmed the positive correlations between PD-L1, VEGF, or MVD. Our findings provided evidence supporting new therapeutic approaches including combinations of anti-PD-L1/PD-1 and anti-VEGF therapy in addition to the current standard regimen for cHL.