TMIC-56. Spatial multi-omics data reveals immune landscape and tertiary lymphoid structures in intracranial germ cell tumors

Abstract Intracranial germ cell tumors (IGCTs) encompass several histologic subtypes, each characterized by distinct morphologies and varying therapeutic outcomes, yet their immune landscape remains poorly understood. To elucidate the immune microenvironment associated with these tumors, we first obtained four samples with paired spatial transcriptomics (Visium HD) and proteomics (CODEX), as well as two additional samples with only spatial transcriptomics data to study the immune microenvironment in different histologic regions. Our observations revealed a diverse immune pattern across IGCT tissue types. Notably, we observed the remarkable presence of tertiary lymphoid structure (TLS) within the IGCTs. Specifically, intratumoral TLS was most abundant and mature in teratoma, germinoma, and their respective components in mixed GCT, whereas yolk sac tumor (YST) exhibited no intratumoral TLS, with only a few peripheral TLS noted. To confirm and extend these findings in additional cases, we analyzed IGCT bulk RNA-seq data, including mature teratomas, immature teratomas (IMT), germinomas, YSTs, and mixed GCTs. Our analysis indicated that germinoma, mixed GCT, and teratoma exhibited both the highest TLS signature scores and the highest abundance of T cells and B cells, while YST and IMT had the least. Additionally, we noticed that the high abundance of B cells and T cells was driven by multiple clones rather than oligoclonal expansion. These findings provide valuable insights into the immune landscape of IGCTs, highlighting the potential for targeted immunotherapies.