Abstract 6171
Background
Clinical trials using immune checkpoint inhibitors (ICPIs) against immune inhibitory receptor ligand 1 (PD-L1) have failed to show clinical benefit for glioblastoma (GBM) patients. This is likely due to multiple factors, including but not limited to, the immunologically cold GBM microenvironment lacking effector immune cells. PD-L1 expression in tumour cells can be regulated by epidermal growth factor receptor/janus kinase 2 (EGFR/JAK2) signalling that might weaken the antitumor immune response by increasing PD-L1 level. Furthermore, EGFR is mutationally activated in approximately 50% of GBMs. Therefore, we analysed changes in EGFR and PD-L1 expression levels in the intraoperative specimens obtained from patients diagnosed with primary GBMs.
Methods
In total, 27 patients with newly diagnosed GBM underwent surgery and were investigated for mRNA and protein expression level either of Ki67, EGFR/EGFRvIII and PD-L1 by quantitative reverse transcription-PCR (qRT-PCR) or immunohistochemistry (IHC).
Results
EGFR overexpression (IHC H-score > 200 [0-300]) was detected in 8/27(30%) specimens as assessed by IHC, whereas 25/27 samples (93%) showed increased EGFR mRNA expression, suggesting a higher sensitivity of qRT-PCR analysis. Of the 25, 10 patients were harbouring EGFRvIII mutation. PD-L1 protein expression (2+ and 3+ staining in > 5% cells) was present in 16/27(60%) samples, of which concurrent elevation of PD-L1 and EGFR mRNA copy numbers was seen in 9/16 samples. In contrast, IHC revealed EGFR overexpression in only 2/16 PDL-1 positive patients. Ki67 staining revealed great variety in proliferation status of the GBMs, with a median Ki67 index of 30 (range 10-62).
Conclusions
Collectively, these results confirm that primary GBMs are characterised by a considerable heterogeneity of EGFR, EGFRvIII and PD-L1 expressions at both mRNA and protein levels. The PD-L1 mRNA expression was found to be associated with EGFR mRNA copy number only in small group of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NCNOPUS13#2017/25/B/NZ5/00039, KNW-1-108/N/8/O.
Disclosure
All authors have declared no conflicts of interest.
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