TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas
Abstract Objective TERT is the most frequently mutated gene in adult glioblastomas (GBMs) defined by the 2021 World Health Organization classification system. The present study aims to explore differences in clinical characteristics and immune microenvironment between TERT mutant and wild-type GBM....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-08-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-023-00760-w |
| _version_ | 1797558818785198080 |
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| author | Feng Tang Xi Chen Jin-Sheng Liu Zhen-Yuan Liu Jin-Zhou Yang Ze-Fen Wang Zhi-Qiang Li |
| author_facet | Feng Tang Xi Chen Jin-Sheng Liu Zhen-Yuan Liu Jin-Zhou Yang Ze-Fen Wang Zhi-Qiang Li |
| author_sort | Feng Tang |
| collection | DOAJ |
| description | Abstract Objective TERT is the most frequently mutated gene in adult glioblastomas (GBMs) defined by the 2021 World Health Organization classification system. The present study aims to explore differences in clinical characteristics and immune microenvironment between TERT mutant and wild-type GBM. Methods Three GBM-related cohorts consisting of 205 GBM patients in our cohort, 463 GBM patients without immune checkpoint inhibitor(ICI) therapy and 1465 tumour patients (including 92 GBM cases) receiving ICI treatment in the MSK cohort were included. Retrospective analysis and immunohistochemistry assay were used for investigating the local (including tumour cells, local immune cells, and seizures) and systemic (including circulating immune cells, coagulation-related functions, and prognosis) effects of TERT mutations. Besides, differences in genetic alterations and immunotherapy responses between TERT mutant and wild-type GBMs were also explored. Results We found that TERT mutant and wild-type GBMs possessed similar initial clinic symptoms, circulating immune microenvironment and immunotherapy response. With respect to that in TERT wild-type GBMs, mutations in TERT resulted in higher levels of tumour-infiltrating neutrophils, prolonged coagulation time, worse chemotherapy response and poorer overall survival. Conclusion Mutations in TERT alter the local immune environment and decrease the sensitivity of GBM to chemotherapy. |
| first_indexed | 2024-03-10T17:36:46Z |
| format | Article |
| id | doaj.art-aba4aa8d441845c89a4fab9a1fa5d22f |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-03-10T17:36:46Z |
| publishDate | 2023-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-aba4aa8d441845c89a4fab9a1fa5d22f2023-11-20T09:50:30ZengSpringerDiscover Oncology2730-60112023-08-0114111110.1007/s12672-023-00760-wTERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomasFeng Tang0Xi Chen1Jin-Sheng Liu2Zhen-Yuan Liu3Jin-Zhou Yang4Ze-Fen Wang5Zhi-Qiang Li6Brain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityBrain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityDepartment of Physiology, Wuhan University School of Basic Medical SciencesBrain Glioma Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan UniversityAbstract Objective TERT is the most frequently mutated gene in adult glioblastomas (GBMs) defined by the 2021 World Health Organization classification system. The present study aims to explore differences in clinical characteristics and immune microenvironment between TERT mutant and wild-type GBM. Methods Three GBM-related cohorts consisting of 205 GBM patients in our cohort, 463 GBM patients without immune checkpoint inhibitor(ICI) therapy and 1465 tumour patients (including 92 GBM cases) receiving ICI treatment in the MSK cohort were included. Retrospective analysis and immunohistochemistry assay were used for investigating the local (including tumour cells, local immune cells, and seizures) and systemic (including circulating immune cells, coagulation-related functions, and prognosis) effects of TERT mutations. Besides, differences in genetic alterations and immunotherapy responses between TERT mutant and wild-type GBMs were also explored. Results We found that TERT mutant and wild-type GBMs possessed similar initial clinic symptoms, circulating immune microenvironment and immunotherapy response. With respect to that in TERT wild-type GBMs, mutations in TERT resulted in higher levels of tumour-infiltrating neutrophils, prolonged coagulation time, worse chemotherapy response and poorer overall survival. Conclusion Mutations in TERT alter the local immune environment and decrease the sensitivity of GBM to chemotherapy.https://doi.org/10.1007/s12672-023-00760-wTERTGlioblastomasImmune microenvironmentImmunotherapy |
| spellingShingle | Feng Tang Xi Chen Jin-Sheng Liu Zhen-Yuan Liu Jin-Zhou Yang Ze-Fen Wang Zhi-Qiang Li TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas Discover Oncology TERT Glioblastomas Immune microenvironment Immunotherapy |
| title | TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas |
| title_full | TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas |
| title_fullStr | TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas |
| title_full_unstemmed | TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas |
| title_short | TERT mutations-associated alterations in clinical characteristics, immune environment and therapy response in glioblastomas |
| title_sort | tert mutations associated alterations in clinical characteristics immune environment and therapy response in glioblastomas |
| topic | TERT Glioblastomas Immune microenvironment Immunotherapy |
| url | https://doi.org/10.1007/s12672-023-00760-w |
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