Abstract
Pure germinomas are pathologically composed by large polygonal undifferentiated cells, accompanied by infiltrating small lymphocytes. Tumor immunity in intracranial germinomas have not been studied well and their role remains unclear. This study aimed to evaluate the clinical value of tumor immunity in intracranial germinomas. We investigated the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) in 8 patients of intracranial germinomas by immunohistochemistry to analyze the association with their clinical courses and radiological features. We divided the patients into group with more than one year from onset to diagnosis as long-term onset group (LTOs), and the group with less than one year as short-term onset group (STOs). Three patients are in LTOs and five patients are in STOs. Median duration from onset to diagnosis in LTOs is 35 months (29–47), while median duration in STOs is 5.1 months (0.5–10). Mortality and recurrence were not observed in all patients. Radiological analysis showed that tumor locations in LTOs are relatively atypical and tumor size in LTOs is smaller than in STOs. TILs in LTOs are having higher expression than STOs. PD-L1 expression was observed in all 8 tumors. CD3, CD8 and PD-1 expressions were observed in all TILs. The ratio of PD-L1 positive-tumor cells was lower in LTOs than in STOs (p=0.012). CD8+ TIL density is higher in LTOs (p=0.003), whereas PD-1/CD8 ratio is lower in LTOs (p=0.047). Our data suggest that PD-1/PD-L1 pathway is associated with pathogenesis and tumor growth of germinomas, therefore immune checkpoint molecule inhibitors against PD-1/PD-L1 may be effective for refractory germinomas.