Background
Ovarian germ cell tumours comprise 28% of all diagnosed ovarian cancers and malignant germ cell tumours specifically account for around 13% in Saudi Arabia. Although most of germ cell tumour patients have high survival rate, tumour recurrence patients have poor prognosis and presented much more aggressive and chemo resistant tumours. The use of immunotherapeutic agents such as PD-L1/PD-1 inhibitors for ovarian germ cell tumours remains very limited because of inadequate studies that describe the immunological characteristics in these tumours. This study is the first to investigate PD-L1 expressions in ovarian germ cell tumours and explore the role of PD-L1 expression in tumour microenvironment cells and genetic alterations.
Methods
A total of 34 ovarian germ cell tumours were collected from pathology archives. The collected tumour tissues included ten dysgerminomas, five yolk sac tumours, five immature teratomas, one mature teratoma, and the remaining were mixed germ cell tumours. The tumours were analysed using immunohistochemistry analysis to determine PDL-1 expressions, immune cell infiltration and cancer stem cells populations and their correlation with the clinical outcome. Further, the genetic alterations in different subtypes of germ cell tumours were correlated with PDL-1 expressions and the clinical outcome. Datasets for testicular germ cells were retrieved from TCGA and PanCancer Atlas and analysed using cBioportal (cbioportal.org).
Results
We found that dysgerminoma is highly expressing PDL-1 and associated with high infiltrating lymphocytes and stem cell markers compared to yolk sac tumour. In addition, dysgerminoma/Seminoma have high PDL-1 expressions are associated with high genetic alterations and better prognosis compared to PDL-1 negative yolk Sac.
Conclusions
Our findings are likely to help improve knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumour patients and risk factors for resistance that are mediated by the tumour microenvironment cells.
Ethics Approval
This retrospective study was approved by King Fahad Specialist Hospital’s Institutional Review Board (IRB) in Dammam; (IRB# ONC0340)