Analysis of PD‐L1 expression and T cell infiltration in different molecular subgroups of diffuse midline gliomas

Abstract

Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies.

Immunotherapy: A Potential Approach for High-Grade Spinal Cord Astrocytomas

“…In CNS malignancies, tumor molecules can avoid detection by recruiting and coordinating T lymphocytes, and transform the immune system from protective to toxic ( 10 ). In spinal cord, the expression rate of PD-L1 is about 20% according to one study ( 11 ). Clinical trials targeting immune checkpoints have been carried out in intracranial gliomas, although the results have not been satisfactory and the study of spinal astrocytomas is still in the blank.…”

Analysis of Histomorphological/molecular Association and Immune Checkpoint Regulators in Epithelioid Glioblastoma and Pleomorphic Xanthoastrocytoma: Are These Tumors Potential Candidate for Immune Checkpoint Blockade

“…Staining for p53 was graded as 0 if no cells stained; 1 + if 0-10% stained; 2 + if 10-50% stained and 3 + if > 50% stained. Grade 2 + and above was considered positive [21]. For H3K27M expression, intense nuclear staining in more than 80% cells was taken as positive (21).…”

“…Grade 2 + and above was considered positive [21]. For H3K27M expression, intense nuclear staining in more than 80% cells was taken as positive (21). For IDH, combined cytoplasmic and nuclear staining was interpreted as immunopositive and for ATRX expression; only nuclear staining was considered for evaluation.…”

Prognostic value of tumor-infiltrating lymphocytes in gliomas: A Systematic Review

“…Non-related articles, cases, and reviews were excluded. Eight articles were nally identi ed as eligible studies for further assessment [9][10][11][12][13][14][15]22 .…”

“…Recently, TILs have also gained attentions in the prognosis of gliomas. However, some studies indicated that TILs were good biomarker for gliomas [9][10][11][12][13][14] while some studies revealed that no signi cant correlation was observed between TILs and gliomas 9,10,13,15 . In order to reach an agreement, we systematically reviewed the studies focused on glioma and TILs.…”