The clinical significance of T cell infiltration and immune checkpoint expression in central nervous system germ cell tumors

Primary central nervous system germ cell tumors (CNS GCTs) are rare intracranial malignancies, and their tumor microenvironment plays a crucial role in tumor initiation and progression. However, the specific characteristics of the immune microenvironment and their clinical significance remain poorly understood.

Our study highlighted the distinct characteristics of T cell infiltration and the significant expression of immune checkpoints in CNS GCTs, revealing the highly heterogeneous and immunosuppressive nature of the tumor microenvironment. PD-1 expression was identified as an independent prognostic predictor, offering a foundation for enhancing risk stratification in CNS GCT patients. These findings also support the potential for future clinical applications of immune checkpoint inhibitors, such as PD-1 monoclonal antibodies.

This study included 93 paraffin-embedded tissue samples from 90 patients diagnosed with CNS GCTs. Immunohistochemistry and immunofluorescence staining were used to assess the infiltration patterns of T cell subsets (CD3+, CD4+, CD8+, Foxp3+) and the expression levels of immune checkpoints (CTLA-4, PD-1, PD-L1). Additionally, the study explored the relationship between these immune features and the patient's clinical characteristics and prognosis.

The study revealed that germinomas exhibited significantly higher infiltration of CD4+ and Foxp3+ T cells compared to non-germinomatous GCTs (NGGCTs). Additionally, CTLA-4 expression was detected in 58.06% of cases, while PD-1 and PD-L1 were expressed in over 90%, with higher CTLA-4 levels in germinomas and elevated PD-L1 levels in NGGCTs. T cell infiltration was positively correlated with immune checkpoint expression, particularly in germinomas. The results also highlighted the strong immunosuppressive nature of the CNS GCTs' tumor microenvironment. Furthermore, T cell infiltration and immune checkpoint expression were closely associated with clinical characteristics and prognosis. Notably, PD-1 expression was identified as an independent prognostic factor for progression-free survival (PFS) and recurrence-free survival (RFS).