ESMO 2017-PDL1 AS PROGNOSTIC FACTOR IN GLIOBLASTOMA

The intratumoural staining pattern of PD-L1 and the intensity of PD-1 staining in tumour infiltrating lymphocytes (TILs) emerged as potentially positive prognostic factors in patients with glioblastoma, according to findings from a retrospective analysis presented at ESMO 2017, the Annual Congress of the European Society for Medcial Oncology in Madrid, Spain.

Glioblastoma is the malignancy most commonly diagnosed within the brain and carries a poor prognosis.

Lead author Didem Şener Dede, Associate Professor in the Department of Medical Oncology, Ankara Yıldırım Beyazıt Universtiy Faculty of Medicine in Ankara, Turkey and colleagues quantitated the degree of  PD-L1 and  PD-1 expression, as well as CD4-positive and CD8-positive TILs, and isocitrate dehydrogenase (IDH-1) mutation. In addition, they evaluated the value of expression levels as prognostic factors of response following surgery and chemoradiotherapy in patients with glioblastoma.

The retrospective study included 90 patients who were newly diagnosed with glioblastoma and underwent surgery between February 2006 to February 2017 at institutions throughout Ankara. PD-L1, PD-1 expression, CD4-positive and CD8-positive TILs, and IDH-1 mutation were assessed in the patients’ tumour specimens. IDH-1 mutation analysis was done by real time PCR, and PD-L1 and PD-1 levels were assessed by  immunohistochemistry using the Ventana® antibody (clon-SP263, ROCHE).

For PD-1, PD-L1, CD4, CD8 TILs staining intensity was graded as low, moderate, dense and estimated in percents’ samples. The cut off value set ≥5% staining as the threshold for PD-L1, PD-1 positivity.

The density of TILs in the intratumoral perivascular fields was positively associated with PD-L1 expression

Dense perivasculer and moderate intratumoral staining of CD4 TILs. 

© Didem Şener Dede.

Membranous staining pattern of PD-L1. 

© Didem Şener Dede. 

Diffuse / fibrillary staining pattern of PD-L1.

© Didem Şener Dede. 

The study included 90 patients with glioblastoma having a mean (standard deviation) age of 57 (± 12.3) years and 63.3 % of the patients were male. Chemoradiotherapy plus chemotherapy with temozolamide following surgery had been admnistered to approximately half (53.3%) of patients.

Two different staining patterns of PD-L1 expression were described as diffuse fibrillary in 29 (32.2%) samples and membranous staining in 15 (16.7%) of samples. IDH-1 mutation was detected in 30 (33%) patients’ samples and dense PD-1 staining was seen. Intense staining of TILs in the perivascular field was observed, which, according to the authors, is rarely found in the intratumoral area.

By Kaplan Meier, Cox regression tests and SPSS 23, the density of TILs in the intratumoral/ perivascular fields positively associated with PD-L1 positivity (r=0.46; p< 0.0001). The intensity of TILs in perivascular areas was significantly lower in tumours that were negative for PD-L1 expression compared to PD-L1-positive tumours (p < 0.001).

No association was found between IDH-1, PD-L1, and TILs. No significant association was found between survival and sex (log rank p = 0.78), PD-L1 positivity (log rank p = 0.13), and IDH-1 mutation status (log rank p = 0.64).

The presence of dense perivascular PD-1-positive TILs was found to be a positive prognostic factor as was dense membranous PD-L1 staining, whereas advanced age emerged as a negative independent prognostic factor by multivariate analysis.

Conclusions

The authors concluded that the staining pattern of PD-L1 and the density of PD-1 expression in TILs may have prognostic importance in patients with newly diagnosed glioblastoma.

M.J. van den Bent of The Brain Tumor Center at Erasmus MC Cancer Center, Rotterdam, the Netherlands, who discussed the study findings pointesd out in term of PD-L1 expression status on different staining patterns: cytoplasmic, membranous, diffuse/fibrillary… PD-L1 can be expressed by both tumour and inflammatory cells within the tumour microenvironment, with unknown relative importance of either. There is no consensus to the relevance of geographic patterns of expression (e.g. proximity of PD-L1 to immune infiltrating lymphocytes, membranous vs cytoplasmic. PD-L1 positivity is found to indicate favourable, unfavourable, or no relationship with prognosis, and variable correlations with histology and mutation status.