Tumor immune microenvironment is associated with the growth of intracranial germinomas

Introduction: The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear. Methods: We investigated the expression of programed cell death-1 (PD-1), programed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) in 8 patients who had intracranial germinomas with sufficient tumor tissue by immunohistochemistry, to analyze the associations between their clinical courses and radiological features. The 8 patients were categorized based on the duration between symptom onset and pathological diagnosis into the long-term onset (LTO) group (> 1 year of symptoms) and the short-term onset (STO) group (< 1 year of symptoms). Results: Three patients belonged to the LTO group and 5 patients to the STO group. Compared with STO tumors, LTO tumors were significantly associated with a lower ratio of PD-L1–positive tumor cells (p = 0.012), higher number of infiltrating CD3- and CD8-positive lymphocytes (p = 0.016, 0.003, respectively), and lower ratio of PD-1–positive cells per CD8-positive lymphocytes (p = 0.047). LTO germinomas were significantly smaller in size than STO tumors, not associated with hydrocephalus, and tended to be present in patients with older age at diagnosis and atypical tumor location. Conclusions: Our data suggest that the tumor immune microenvironment, including PD-1/PD-L1 signaling, is associated with the growth of intracranial germinomas.