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. 2020 Oct 27;11:5424. doi: 10.1038/s41467-020-19193-y

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Example of a pre-operative T1-weighted fat-saturated post-contrast MRI obtained from a GBM patient included in the study cohort as in b; necrotic core (asterisk); tumor (arrow). b Correlation analyses of pre-operative T1-weighted MRI-identified necrosis-to-tumor volumetric ratios and peripheral neutrophil count reported in blood differentials in a GBM patient cohort (n = 75 human subjects), Pearson’s correlation coefficient test. c Representative H&E-stained formaldehyde-fixed paraffin-embedded human GBM section containing the necrotic zone. A total of 45 patients were examined with similar observations. d Comparison of absolute numbers of neutrophils/high-power field among cellular tumor (CT), necrosis (N), and CT-N interface zones (CT/N) in human GBM sections obtained from a deceased patient cohort (n = 45 patients); Brown-Forsythe and Welch one-way ANOVA tests. e Chromogenic immunodetection of human granulocyte marker, CD66b, in a formaldehyde-fixed paraffin-embedded, human GBM brain section obtained from the study cohort used for quantification in d. The outlined areas are enlarged and shown on the right. Specimens from three different patients were examined independently with similar observations. f Kaplan–Meier survival curve of the patient cohort shown in b; all deceased patients (n = 37 patients) from this cohort were included for survival analysis. Patients were separated into two groups by median radiographically identified necrosis-to-tumor (N/T) volumetric ratios; two-sided log-rank test. g Kaplan–Meier survival curve of the patient cohort as shown in d; all patients from the cohort shown in d were included in this survival analysis (n = 45 patients). Patients were separated into two groups by median absolute neutrophil count/high-power field in necrotic region obtained from their diagnostic H&E-stained sections. Two-sided log-rank test. h Current proposed model of how TANs contribute to augmenting GBM necrosis development to its fullest extent via neutrophil-mediated ferroptotic tumor cell death. All scale bars are in μm, except in Fig. 8a, whose scale bar is in cm. Source data are provided as a Source Data file.