Abstract

Abstract BACKGROUND Germinoma is the commonest CNS germ cell tumor. An important histological feature is prominent immune cell infiltrates. The composition of such immune cell infiltrates remains under-investigated in the literature. MATERIAL AND METHODS We collected a cohort of 40 cases of intra-cranial germinomas and examined the clinical and histopathological features. The tumor infiltrating immune cells were characterized by immunohistochemistry and image analysis. RESULTS Across the cohort, the mean positivity ± SE of CD3-positive T cell and CD20-positive B cells was 31.2% ± 3.1% and 15.2% ± 2.2%, respectively (p<0.001). The mean positivity of CD4-positive T helper cell and CD8-positive cytotoxic T cell was 19% ± 2.3% and 14.3% ± 1.7%, respectively (p<0.001). PD-L1 expression was detected in 50% of the cases and was observed exclusively in immune cells but not in neoplastic cells. Germinomas with positive PD-L1 expression had significantly more abundant CD3-positive T cells (p=0.001), CD4-positive T helper cells (p<0.001) and CD8-positive cytotoxic T cells (p=0.004) as compared with those lacking PD-L1 expression. Immunostain for HLA-A and HLA-B revealed loss of HLA class I expression occurring in 92.5% of the germinomas. Loss of HLA class I expression was associated with less abundant CD3-positive T cells (p=0.04). CONCLUSION Taken together, the predominant T cells infiltrate and PD-L1 expression suggest anti-PD-L1 therapeutic agents as potential novel treatment option for germinoma patients. The loss of HLA class I may represent one of the mechanisms for tumor immune escape in germinoma.

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