Edema is a hallmark of inflammation. Therefore, we explored the correlation of the peritumoral edema with tumor-infiltrating lymphocyte (TIL) density in newly diagnosed glioblastoma.
133 patients (60.9% male; 39.1% female) with histologically verified newly diagnosed glioblastoma were included in this study. The volume of peritumoral non-enhancing T2-hyperintense signal abnormalities was measured to quantify edema and non-enhancing tumor tissue. CD3+, CD8+ and PD-1+ TIL densities were analyzed using immunohistochemistry and tissue phenomics software.
Median perifocal edema volume was 84200 mm3 (range: 442.4 – 254700). Median TIL densities were 74.7 cells/mm2 for CD3+ (range: 3.1 – 1071.4), 29.6 cells/mm2 for CD8+ (range: 3.0 – 290.3) and 13.6 cells/mm2 for PD-1+ TILs (range: 1.6 – 141.5). Strong correlation between CD3+ and CD8+ TIL densities was observed (Spearman’s r = 0.784, p < 0.001), furthermore PD-1+ TIL density correlated with CD3+ (r = 0.591, p < 0.001) and CD8+ (r = 0.532, p < 0.001) TIL densities. Larger than median perifocal edema volume correlated with higher CD8+ (p = 0.036) and tendentially higher PD-1+ TIL densities (p = 0.199), but not with CD3+ TIL density (p = 0.883). Among 84 patients with known methylguanine methyltransferase (MGMT) promoter methylation status, 33 (39.3%) patients with MGMT promoter hypermethylation had less perifocal edema than their unmethylated counterparts (n = 51/84, 60.7%; median: 84200 mm3 vs. 122400 mm3; p = 0.047), while there was no significant difference in CD3+, CD8+ and PD-1+ TIL density according to MGMT promoter methylation status.
Peritumoral non-enhancing T2-hyperintense signal abnormality volumes correlate with the density of intra-tumoral cytotoxic T cells in newly diagnosed glioblastoma and may serve as “immuno-radiomic” surrogate parameter.
The authors.
Roche (unrestricted grant), Medical University of Vienna (research budget).
M. Preusser: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Gerson Lehrman Group (GLG); Honoraria (self), Advisory/Consultancy: CMC Contrast; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Mundipharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: BMJ Journals; Honoraria (self), Advisory/Consultancy: MedMedia; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Medahead; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Tocagen; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Novocure. A.S. Berghoff: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: AbbVie. All other authors have declared no conflicts of interest.