Investigation of the relationship between immune checkpoints and mismatch repair deficiency in recurrent and nonrecurrent glioblastoma


Çakir E., SayĞin İ. , Ercİn M. E.

Turkish journal of medical sciences, vol.51, no.4, pp.1800-1808, 2021 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 51 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.3906/sag-2010-166
  • Title of Journal : Turkish journal of medical sciences
  • Page Numbers: pp.1800-1808
  • Keywords: Glioblastoma, mismatch repair, programmed cell death protein ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), microsatellite instability, LONG-TERM SURVIVAL, DEATH-LIGAND 1, MICROSATELLITE INSTABILITY, EXPRESSION, BLOCKADE, GLIOMA, TUMORS, MECHANISMS, MULTIFORME, RESISTANCE

Abstract

Background/aim: Microsatellite instability tests and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) in the immune checkpoint pathway are the tests that determine who will benefit from immune checkpoint inhibitor therapy. We aimed to show the expression of DNA mismatch repair proteins and PD-1/PD-L1 molecules that inhibit immune checkpoints, to explain the relationship between them, and to demonstrate their predictive role in recurrent and nonrecurrent glioblastoma. Materials and methods: We analyzed 27 recurrent and 47 nonrecurrent cases at our archive. We performed immunohistochemical analysis to determine expressions of PD-1, PD-L1, and mismatch repair proteins in glioblastoma. We evaluated the relationship between these two group and compared the results with the clinicopathological features. Results: The mean age of diagnosis was significantly lower in recurrent glioblastoma patients. Median survival was longer in this group. We found that PD-L1 expression was reduced in recurrent cases. Additionally, recurrent cases had a significantly higher rate of microsatellite instability. Loss of PMS2 was high in both group but was substantially higher in recurrent cases. Conclusion: The presence of microsatellite instability and low PD-L1 levels, which are among the causes of treatment resistance in glioblastoma, were found to be compatible with the literature in our study, with higher rates in recurrent cases. In recurrent cases with higher mutations and where immunotherapy resistance is expected less, low PD-L1 levels thought that different combinations with other immune checkpoint inhibitors can be tried as predictive and prognostic marker in GBM patients.