P04.09 Tumor infiltrating lymphocytes and programmed death ligand 1 (PD-L1) expression in diffuse and anaplastic gliomas

Abstract

AbstractBackground:Immune modulatory therapies have shown impressive and durable responses in various extracranial malignancies. An immunologically active tumor microenvironment as defined by presence of tumor infiltrating lymphocytes (TILs) or expression of PD-L1 have been proposed as predictive for response to immune checkpoint inhibitors.Methods:TILs and PD-L1 expression were analyzed with immunohistochemical methods in a retrospective cohort from Vienna (Vienna cohort: 25 diffuse low-grade gliomas (LGG; WHO grade 2) and 20 anaplastic gliomas (AG, WHO grade 3)). Histology encompassed 21/45 (46.7%) astrocytoma, 11/45 (24.4) mixed oligoastrocytomas and 13/45 (28.9%) oligodendroglioma. 36/44 (81.8%) specimens presented with IDH-R132H mutation (per immunohistochemistry) and 17/42 (40.5%) with 1p19q co-deletion (per FISH). PD-L1 gene expression was further analyzed in 205 WHO grade II and 225 WHO grade III cases from the Cancer Genome Atlas (TCGA).Results:In the Vienna cohort, CD3+ TIL infiltration was found in 13/25 (52.0%) LGG and 11/20 (55.0%) AG, CD8+ in 9/25 (26.0%) and 10/20 (50.0%), CD45RO+ in 1/25 (4.0%) and 5/20 (25.0%), FOXP3+ in 1/25 (4.0%) and 6/20 (30.0%) and PD-1+ TILs in 0/25 (0%) LGG and 0/20 (0%) AG. CD45RO+ TILs (p=0.039) and FOXP3+ TILs (p=0.0317) were more frequently observed among AG compared to LGG. PDL1 expression of tumor cells was found in 13/25 (52.0%) LGG and 11/20 (55.0%) AG. 6/25 (24.0%) LGG and 4/20 (20.0%) AG presented with PD-L1 expression in > 25% of viable tumor cells. IDH-R132H wild type specimens presented more frequently with CD8+ TIL infiltration compared to IDH-R132H mutated specimens (p=0.030). No correlation of other TIL subtypes and PD-L1 expression with IDH mutation status or 1p19q co-deletion was present (p>0.05). In the TCGA cohort, PD-L1 gene expression levels were higher in WHO grade III tumors compared to WHO grade II tumors (p= 3.966e-6). Further, PD-L1 expression levels were higher in IDH wild type specimens compared to IDH mutated specimens (p= 3.086e-6).Conclusion:Sparse TIL infiltrates and PD-L1 expression are commonly found in diffuse gliomas and seem to show some association with histological grade and molecular status.