Central Nervous System Germinomas Express Programmed Death Ligand 1.

Abstract

Immunomodulation and tumor-induced tolerance is one of the central mechanisms in the oncogenesis of malignant and benign neoplasms. While numerous pathways have been described, signaling through the programmed death receptor 1 (PD-1) on T lymphocytes, via activation through its ligand, programmed death ligand 1 (PD-L1) expressed on tumor cells is one of the central pathways involved in tumor-induced tolerance. While the neoplastic component of germinomas of the CNS is the germ cell, these tumors also exhibit an abundance of quiescent tumor-infiltrating lymphocytes. We therefore investigated whether PD-L1 expression may be responsible for germinoma-induced T cell anergy, and if these tumors may be susceptible to immunotherapy. Pathologic specimens obtained from 21 cases of CNS germinomas between 2000 and 2016 were analyzed for the presence of PD-L1 and PD-1 expression by immunohistochemistry. Nineteen of 21 germinomas (90%) harbored germ cell components that stained positively for PD-L1. Positive lymphocyte staining for PD-L1 was evident in 16 cases. PD-1 expression was largely confined to lymphocytes; PD-L1 therefore may contribute to lymphocyte quiescence observed in these tumors. These results raise the possibility that immune checkpoint inhibitors such as nivolumab may have a therapeutic role in future treatment of germinomas.