Pd-l1 expression change at diagnosis and recurrence in high grade glial tumors

Programmed cell death 1 (PD-1) is a transmembrane protein that binds to PD-Ligand 1 (PD-L1) and PD-L2 and expressed by T, B and NK cells. PD-L1 is expressed by glial tumors and tumor associated macrophages and causes immune suppression and tumor progression by binding to PD-1. The aim of this thesis is to determine if PD-L1 expression status changes in recurrent gliomas after chemoradiotherapy and to demonstrate if there is any relationship between survival and PD-L1 expression status in high grade recurrent gliomas. Thirty eight patients with recurrent high grade gliomas who had surgical excision at least two times in Yeditepe University Hospital between December 2005 and March 2016 were included in this retrospective cross-sectional study. Nine patients were excluded because of the lack of appropriate pathology slides for pathologic evaluation. PD-L1 expression was evaluated by an expert pathologist with immunohistochemical methods. Tumor PD-L1 expression was positive in 15 (51.8%) and negative in 14 (48.2% of 29 patients at diagnosis and recurrence. Tumor PD-L1 expression increased in 7 of 29 patients (24.1%), while decreased in 9 of 29 patients (31.1%) in relapsed patients. PD-L1 expression remained stable in 13 of 29 patients (34.4%). Median overall survival time was 23 months for PD-L1 expressing patients and 26 months for non PD-L1 expressing patients in the first diagnosis. PD-L1 expression in tumor associated macrophages was positive in 19 (65.5%) and negative in 10 (34.4%) of 29 patients at first diagnosis. Conversion from PD-L1 expressed status to non PD-L1 expressed status was observed 5 of 19 patients (26.3%), while conversion to positive status was observed in 4 of 10 patients (40%) in relapsed patients. PD-L1 expression in macrophages remained stable in 20 patients (34.4%). Tumor and tumor associated macrophage PD-L1 expressions were negative in 8 patients(27.6%) while anyone of them was positive in 21 patients (72.4%) at first diagnosis. Tumor and tumor associated macrophage PD-L1 expressions were negative in 10 patients(%34.4), while anyone of them was positive 19 patients(65.5%) at recurrent diagnosis. There is no statistically significant change in PD-L1 expression in tumor and tumor associated macrophage and median overall survival between PD-L1 expressed and non expressed patients in recurrent high grade gliomas after chemoradiotherapy. key words: glial tumor, programmed death ligand , PD L1