Tumor Mutation Burden, Expressed Neoantigens and the Immune Microenvironment in Diffuse Gliomas

Guangyang Yu; Ying Pang; Mythili Merchant; Chimene Kesserwan; Vineela Gangalapudi; Abdalla Abdelmaksoud; Alice Ranjan; Olga Kim; Jun S. Wei; Hsien-Chao Chou; Xinyu Wen; Sivasish Sindiri; Young K. Song; Liqiang Xi; Rosandra N. Kaplan; Terri S. Armstrong; Mark R. Gilbert; Kenneth Aldape; Javed Khan; Jing Wu

doi:10.3390/cancers13236092

Cancers (Dec 2021)

Tumor Mutation Burden, Expressed Neoantigens and the Immune Microenvironment in Diffuse Gliomas

Guangyang Yu,
Ying Pang,
Mythili Merchant,
Chimene Kesserwan,
Vineela Gangalapudi,
Abdalla Abdelmaksoud,
Alice Ranjan,
Olga Kim,
Jun S. Wei,
Hsien-Chao Chou,
Xinyu Wen,
Sivasish Sindiri,
Young K. Song,
Liqiang Xi,
Rosandra N. Kaplan,
Terri S. Armstrong,
Mark R. Gilbert,
Kenneth Aldape,
Javed Khan,
Jing Wu

Affiliations

Guangyang Yu: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Ying Pang: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mythili Merchant: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Chimene Kesserwan: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Vineela Gangalapudi: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Abdalla Abdelmaksoud: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Alice Ranjan: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Olga Kim: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Jun S. Wei: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Hsien-Chao Chou: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Xinyu Wen: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Sivasish Sindiri: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Young K. Song: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Liqiang Xi: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Rosandra N. Kaplan: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Terri S. Armstrong: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mark R. Gilbert: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Kenneth Aldape: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Javed Khan: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Jing Wu: Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

DOI: https://doi.org/10.3390/cancers13236092
Journal volume & issue: Vol. 13, no. 23
p. 6092

Abstract

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Background: A consistent correlation between tumor mutation burden (TMB) and tumor immune microenvironment has not been observed in gliomas as in other cancers. Methods: Driver germline and somatic mutations, TMB, neoantigen, and immune cell signatures were analyzed using whole exome sequencing (WES) and transcriptome sequencing of tumor and WES of matched germline DNA in a cohort of 66 glioma samples (44 IDH-mutant and 22 IDH-wildtype). Results: Fourteen samples revealed a hypermutator phenotype (HMP). Eight pathogenic (P) or likely pathogenic (LP) germline variants were detected in 9 (19%) patients. Six of these 8 genes were DNA damage repair genes. P/LP germline variants were found in 22% of IDH-mutant gliomas and 12.5% of IDH-wildtype gliomas (p = 0.7). TMB was correlated with expressed neoantigen but showed an inverse correlation with immune score (R = −0.46, p = 0.03) in IDH-wildtype tumors and no correlation in IDH-mutant tumors. The Antigen Processing and Presentation (APP) score correlated with immune score and was surprisingly higher in NHMP versus HMP samples in IDH-wildtype gliomas, but higher in HMP versus NHMP in IDH-mutant gliomas. Conclusion: TMB was inversely correlated with immune score in IDH-wildtype gliomas and showed no correlation in IDH-mutant tumors. APP was correlated with immune score and may be further investigated as a biomarker for response to immunotherapy in gliomas. Studies of germline variants in a larger glioma cohort are warranted.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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