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Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma

Although the successful clinical trials of immunotherapy show promising strategies for many cancers, its application in glioma has lagged in comparison with the progress seen in other cancers. Both isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions are critical molecular alterations aff...

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Autores principales: Lin, Wanzun, Qiu, Xianxin, Sun, Pian, Ye, Yuling, Huang, Qingting, Kong, Lin, Lu, Jiade J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167204/
https://www.ncbi.nlm.nih.gov/pubmed/34141867
http://dx.doi.org/10.1016/j.omto.2021.04.010
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author Lin, Wanzun
Qiu, Xianxin
Sun, Pian
Ye, Yuling
Huang, Qingting
Kong, Lin
Lu, Jiade J.
author_facet Lin, Wanzun
Qiu, Xianxin
Sun, Pian
Ye, Yuling
Huang, Qingting
Kong, Lin
Lu, Jiade J.
author_sort Lin, Wanzun
collection PubMed
description Although the successful clinical trials of immunotherapy show promising strategies for many cancers, its application in glioma has lagged in comparison with the progress seen in other cancers. Both isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions are critical molecular alterations affecting therapeutic response in lower-grade glioma (LGG). The systematic and comprehensive characterization of the immunological phenotypes with different molecular subtypes is key to improving our understanding and application of immunotherapies in LGG. Here, we collected the RNA-sequencing, somatic mutation, and clinical data from 1,052 patients from The Cancer Genome Atlas and Chinese Glioma Genome Atlas and stratified patients into three genetic subgroups: IDH mutations with 1p/19q codeletions (IDH mut-codel), IDH mutations without 1p/19q codeletions (IDH mut-noncodel), and IDH wild-type. Our evaluations revealed that IDH mutations and 1p/19q codeletions were associated with distinct immunological tumor microenvironments in LGG. In addition, immune cell infiltration, the expression of immune checkpoint and human leukocyte antigen (HLA) gene, and the activity of immune signaling pathways shared gradual increase from IDH mut-codel to IDH wild-type. We further constructed and validated an immune-related prognostic signature that presented high value in predicting the overall survival time in LGG. In conclusion, our study may provide valuable information for immunotherapy strategies in LGG patients.
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spelling pubmed-81672042021-06-16 Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma Lin, Wanzun Qiu, Xianxin Sun, Pian Ye, Yuling Huang, Qingting Kong, Lin Lu, Jiade J. Mol Ther Oncolytics Original Article Although the successful clinical trials of immunotherapy show promising strategies for many cancers, its application in glioma has lagged in comparison with the progress seen in other cancers. Both isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions are critical molecular alterations affecting therapeutic response in lower-grade glioma (LGG). The systematic and comprehensive characterization of the immunological phenotypes with different molecular subtypes is key to improving our understanding and application of immunotherapies in LGG. Here, we collected the RNA-sequencing, somatic mutation, and clinical data from 1,052 patients from The Cancer Genome Atlas and Chinese Glioma Genome Atlas and stratified patients into three genetic subgroups: IDH mutations with 1p/19q codeletions (IDH mut-codel), IDH mutations without 1p/19q codeletions (IDH mut-noncodel), and IDH wild-type. Our evaluations revealed that IDH mutations and 1p/19q codeletions were associated with distinct immunological tumor microenvironments in LGG. In addition, immune cell infiltration, the expression of immune checkpoint and human leukocyte antigen (HLA) gene, and the activity of immune signaling pathways shared gradual increase from IDH mut-codel to IDH wild-type. We further constructed and validated an immune-related prognostic signature that presented high value in predicting the overall survival time in LGG. In conclusion, our study may provide valuable information for immunotherapy strategies in LGG patients. American Society of Gene & Cell Therapy 2021-04-29 /pmc/articles/PMC8167204/ /pubmed/34141867 http://dx.doi.org/10.1016/j.omto.2021.04.010 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Lin, Wanzun
Qiu, Xianxin
Sun, Pian
Ye, Yuling
Huang, Qingting
Kong, Lin
Lu, Jiade J.
Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title_full Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title_fullStr Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title_full_unstemmed Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title_short Association of IDH mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
title_sort association of idh mutation and 1p19q co-deletion with tumor immune microenvironment in lower-grade glioma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167204/
https://www.ncbi.nlm.nih.gov/pubmed/34141867
http://dx.doi.org/10.1016/j.omto.2021.04.010
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