O6.02 * ANALYSIS OF PD1 AND PD-L1 EXPRESSION IN GLIOBLASTOMA

Abstract

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death (PD)1 and PD-ligand (L)1 show promising clinical activity in various solid extracranial cancers. Expression of PD1 on tumor infiltrating T lymphocytes and PD-L1 expression on tumor cells were postulated to have predictive value for the response to PD1/PD-L1 targeting immune checkpoint inhibitors. METHODS: 135 specimens of 117 patients (median age 60, range 21-80); median KPS 90 (range 10-100) with glioblastoma were included. In 18 patients, resection specimens of the first local recurrence in addition to tumor tissue from the initial resection were available. Analyses of PD1, PD-L1, CD3 and CD8 expression were performed by immunohistochemistry and previously published semiquantitative evaluation criteria. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was analyzed using pyrosequencing and a cut-off at 8%. RESULTS: Sparse to moderate density of tumor-infiltrating lymphocytes (TILs) in a total of 100/135 (74.1%) cases (CD3+ 92/135, 68.1%; CD8+ 64/135, 47.4%) was observed. PD1 expression was found on scattered TILs, both within the tumor tissue and in the perivascular compartment, in 20/135 (14.8%) cases. PD-L1 expression was evident on tumor cells and macrophages/microglial cells throughout the tumor tissue with occasional focal accentuation in 116/135 (85.9%) specimens, with 44.5% showing PD-L1 staining of more than 50% of the viable tumor tissue. MGMT methylation was found in 37/99 (37.4%) analyzed specimens. No significant correlation of expression of PD1 or PD-L1 with the density of TILs or MGMT methylation status (p > 0.05) was observed. Younger age (p = 0.009), high KPS (p = 0.035) and MGMT hypermethylation (p = 0.008) showed a significant correlation with favorable overall survival, while TIL density or expression of PD1 (p = 0.783) and PD-L1 (p = 0.866) did not associate with patient outcome. CONCLUSION: PD1 and/or PD-L1 are immunohistochemically detectable in a majority of glioblastoma samples. A clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.