Immunobiological characterization of CNS germinomas

Introduction:

Germinomas are malignant pediatric intracranial germ cell tumors, which are characterized by a massive immune cell infiltrate. Aim of our study was to systematically characterize and quantify these immune cells.

Methods:

Immunohistochemistry was performed on FFPE tissue sections of 30 CNS germinomas using antibodies specific for different immune cell populations. Cells were quantified using an image analysis work station (Definiens Tissue Studio). In situ RNA hybridization (RNAscope, Advanced Cell Diagnostics) was performed targeting PD-L1, IL-10 and IFN-gamma and combined with immunohistochemistry for PD-L1 and CD163.

Results:

Infiltrating immune cells were mainly composed of lymphocytes and macrophages. T cells represented 60%, B cells 37% of lymphocytes. Tumor-associated macrophages were characterized by clusters of activated macrophages expressing PD-L1 and interspersed macrophages expressing CD163. Tumor cells did not express PD-L1. Activity of immunosuppressive mechanisms was further indicated by presence of regulatory T cells, PD-1 expressing lymphocytes and IL-10 expressing cells.

Conclusion:

The strong immune reaction observed in germinomas involves inflammatory (e.g. IFN-gamma expression) as well as suppressive mechanisms, with the latter probably being an adaptive response. Nevertheless, expression of PD-1 and PD-L1 and infiltration of cytotoxic T cells are biomarkers predictive of response to anti-PD-1/PD-L1 therapies, constituting a rationale for new treatment approaches.