Non-specific immunotherapy inhibits angiogenesis – results of the monitoring of serum levels of vascular endothelial growth factor and matrix metalloproteinase 8 in patients with malignant melanoma receiving adjuvant high-dose interferon therapy
Authors:
J. Prošvicová 1; J. Grim 2; J. Kopecký 2; P. Priester 2; I. Slánská 2; P. Trojanová 2; A. Paulík 2; V. Jílková 2; S. Filip 2; Š. Lukešová 1,3; P. Prošvic 1; J. Knížek 4; C. Andrýs 5
Authors‘ workplace:
Onkologické oddělení, Oblastní nemocnice Náchod
1; Klinika onkologie a radioterapie, Fakultní nemocnice Hradec Králové
2; Ústav klinické mikrobiologie, Lékařská fakulta v Hradci Králové, Univerzita Karlova
3; Ústav biofyziky a biostatistiky, Lékařská fakulta v Hradci Králové, Univerzita Karlova
4; Oddělení klinické imunologie, Fakultní nemocnice Hradec Králové
5
Published in:
Epidemiol. Mikrobiol. Imunol. 66, 2017, č. 1, s. 15-23
Category:
Original Papers
Overview
Objective:
Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated.
Material and methods:
We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment.
Results:
To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent.
Conclusions:
Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.
KEYWORDS:
angiogenesis – immunomodulation – interferon alpha-2b – adjuvant therapy – malignant melanoma
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