BIOM-58. HETEROGENEITY OF TSPO PET LABELLING ACROSS GLIOMA ENTITIES

Abstract PET imaging targeting the translocator protein (18kDA) (TSPO) has recently been described to reflect the heterogeneity of the tumor microenvironment. Tracer enrichment patterns might therefore differ between glioma types and bear additional relevant information. We collected a glioma patient cohort with standardized PET imaging, image-guided resection and detailed neuropathological work-up. We previously reported (Weidner et al., Acta Neuropathol Commun 2023, 11:147) that in IDH-wildtype glioblastomas TSPO marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages (TAMs). We now focused on understanding the cellular composition of the TSPO signal in IDH-mutant astrocytomas (n=24) and oligodendrogliomas (n=20). We performed immunohistochemistry and four-plex immunofluorescence to assess TSPO expression along with markers for tumor cells (IDH1-R132H and p53) and TAMs (CD68 and CD11b). The cellular source of TSPO expression was further examined by employing RNA sequencing (RNASeq) and evaluating publicly available single-cell RNA sequencing (scRNA-seq) datasets from Venteicher et al. (Science 2017, 355:eaai8478). TSPO expression in astrocytomas increases with tumor cell content and grade. Both tumor cells and TAMs express TSPO, with interpatient variance mainly resulting from the tumor cells. TSPO expression correlates to TAM signatures and MES-like genes are upregulated in TSPO-high samples. Oligodendrogliomas show the lowest TSPO signal among glioma subtypes, with higher TSPO expression in recurrent tumors. Tumor areas contain a higher proportion of TSPO-positive TAMs compared to tumor cells and in infiltration areas TSPO is related to CD68-positive TAMs. There is no correlation between TSPO expression and TAM signatures nor evidence of an upregulation of MES-like genes in TSPO-high samples. We conclude that -similar to glioblastoma- high TSPO expression in astrocytomas marks prognostically unfavorable tumor cell populations characterized by a high amount of TAMs. In oligodendrogliomas, high TSPO expression is rare, fairly restricted to recurrent tumors and does not seem to result from TAM-tumor cell interactions.