Abstract
BACKGROUND AND OBJECTIVES: Immune checkpoint inhibitors like PDL-1, CTLA-4, STAT-3 and IDO-1 are increasingly evaluated in clinical trials for glioblastoma treatment.. Despite initiation of clinical trials, their expression in newly diagnosed (primary) and recurrent GBM remains unclear. This study aims to address this lacuna. MATERIALS AND METHODS: Protein expression of PDL-1 and CTLA-4 using immunohistochemistry and their correlation with survival was assessed in 60 adult GBM patients. In a cohort of primary(n=23) and recurrent GBM(n=24) patients, protein expression of PDL-1 and CTLA-4 and mRNA expression of STAT-3 and IDO-1 were compared. Paired samples of newly diagnosed GBM and recurrence were analysed in 12 patients. RESULTS: PDL-1 expression was noted in 58.3% of tumors, while CTLA-4 expression was noted in 41.7% of tumors. PDL-1 and CTLA-4 expression did not show survival significance in our study. In comparison cohort, PDL-1 protein expression was lower in recurrent tumors. We noted, for the first time, that, CTLA-4 protein expression was higher in recurrent GBM as compared to primary GBM. STAT-3 and IDO-1 mRNA expression did not differ significantly between primary and recurrent GBM. CONCLUSION: An increase in CTLA-4 expression and no change in IDO-1 and STAT-3 expression at recurrence, identified in our cohort, may likely indicate that only selective inhibitors might be good candidate therapeutic agents in recurrent GBM. We noted that PDL-1 expression is significantly reduced in recurrent GBM. Stratification of immune check point inhibitors therapy in clinical trials based on marker expression could be more effective in novel drug discovery.