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13.07.2020 | Original Article

NF2 mutation status and tumor mutational burden correlate with immune cell infiltration in meningiomas

verfasst von: John W. Rutland, Corey M. Gill, Joshua Loewenstern, Hanane Arib, Margaret Pain, Melissa Umphlett, Yayoi Kinoshita, Russell B. McBride, Joshua Bederson, Michael Donovan, Robert Sebra, Raj K. Shrivastava, Mary Fowkes

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 1/2021

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Abstract

Background

The tumor microenvironment is an emerging biomarker of underlying genomic heterogeneity and response to immunotherapy-based treatment regimens in solid malignancies. How tumor mutational burden influences the density, distribution, and presence of a localized immune response in meningiomas is unknown.

Methods

Representative hematoxylin and eosin slides were reviewed at 40X to assess for the density of inflammatory cells. Lymphocytes and macrophages were quantified in the following ordinal manner: 0 = not present, 1 = 1–25 cells present, and 2 = greater than 26 cells present. Immune cell infiltrate grade was scored for both scattered and aggregated distributions. Next generation targeted sequencing was performed on all meningiomas included in this study.

Results

One hundred and forty-five meningiomas were evaluated in this study. Lymphocytes were observed in both scattered (95.9%) and aggregated (21.4%) distributions. A total of 115 (79.3%) meningiomas had 1–25 scattered lymphocytes, and 24 (16.6%) had > 25 scattered lymphocytes, and 6 (4.1%) had no scattered lymphocytes. Twenty (13.8%) meningiomas had 1–25 aggregated lymphocytes. Eleven (7.6%) had > 25 aggregated lymphocytes and 114 (78.6%) had no aggregated lymphocytes. Six (4.1%) meningiomas had 1–25 aggregated macrophages, 5 (3.4%) had > 25 aggregated macrophages, and 134 (92.4%) had no aggregated macrophages. Density of aggregated lymphocytes and aggregated macrophages were associated with higher tumor grade, P = 0.0071 and P = 0.0068, respectively. Scattered lymphocyte density was not associated with meningioma grade. The presence of scattered lymphocytes was associated with increased tumor mutational burden. Meningiomas that did not have scattered lymphocytes had a mean number of single mutations of 2.3 ± 2.9, compared with meningiomas that had scattered lymphocytes, 6.9 ± 20.3, P = 0.03. NF2 mutations were identified in 59 (40.7%) meningiomas and were associated with increased density of scattered lymphocytes. NF2 mutations were seen in 0 (0%) meningiomas that did not have scattered lymphocytes, 46 (40.0%) meningiomas that had 1–25 scattered lymphocytes, and 13 (54.2%) meningiomas that had > 25 scattered lymphocytes, P = 0.046.

Conclusions

Our findings suggest that distribution of immune cell infiltration in meningiomas is associated with tumor mutational burden. NF2 mutational status was associated with an increasing density of scattered lymphocytes. As the role of immunotherapy in meningiomas continues to be elucidated with clinical trials that are currently underway, these results may serve as a novel biomarker of tumor mutational burden in meningiomas.

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Titel: NF2 mutation status and tumor mutational burden correlate with immune cell infiltration in meningiomas
verfasst von: John W. Rutland
Corey M. Gill
Joshua Loewenstern
Hanane Arib
Margaret Pain
Melissa Umphlett
Yayoi Kinoshita
Russell B. McBride
Joshua Bederson
Michael Donovan
Robert Sebra
Raj K. Shrivastava
Mary Fowkes
Publikationsdatum: 13.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 1/2021
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02671-z

Springer Medizin

NF2 mutation status and tumor mutational burden correlate with immune cell infiltration in meningiomas