Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up
Abstract Purpose Immunotherapy is a promising treatment for cancers but should be optimized for malignant gliomas. Because of immune privilege feature of the brain, local administration of immunotherapy may be a promising strategy for malignant glioma treatment. Identification of patients who may be...
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BMC
2024-12-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-024-00676-2 |
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| author | Hao Duan Zhenqiang He Zhenghe Chen Yukun Chen Wanming Hu Ke Sai Xiangheng Zhang Jianchuan Xia Yongqiang Li Ranyi Liu Chaowei Zou Zhongping Chen Yonggao Mou |
| author_facet | Hao Duan Zhenqiang He Zhenghe Chen Yukun Chen Wanming Hu Ke Sai Xiangheng Zhang Jianchuan Xia Yongqiang Li Ranyi Liu Chaowei Zou Zhongping Chen Yonggao Mou |
| author_sort | Hao Duan |
| collection | DOAJ |
| description | Abstract Purpose Immunotherapy is a promising treatment for cancers but should be optimized for malignant gliomas. Because of immune privilege feature of the brain, local administration of immunotherapy may be a promising strategy for malignant glioma treatment. Identification of patients who may benefit from local immunotherapy is essential. Methods We retrospectively reviewed the clinicopathological characteristics and outcomes of six malignant glioma patients who received local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor resection cavity. Profiles of tumor genome, transcriptome and immune microenvironment were also investigated by genomic target sequencing, RNA sequencing, electrochemiluminescence assay and immunohistochemistry (IHC) staining. Results Four patients died from tumor progression and the overall survival ranged from 10.0 to 33.9 months. Remarkably, two patients, including one diagnosed as diffuse hemispheric glioma H3 G34-mutant (G34-DHG, WHO grade 4) and the other diagnosed as astrocytoma (IDH1 mutation, WHO grade 3) survived more than 20 years without evidence of recurrence. The distinctive clinical feature of the two long-term survivors was tumor gross total resection (GTR) before CIK therapy. NTRK1 mutation was uniquely present and 353 genes were differentially expressed in the long-term survivors compared with the short-term survivors. These differential expression genes were highly associated with immune function. Electrochemiluminescence assay and IHC staining revealed higher expressions of cytokines and lower infiltrations of tumor-associated macrophages in the tumors of the long-term survivors. Conclusion These findings suggest that certain patients diagnosed as malignant gliomas, including G34-DHG (WHO grade 4), can acquire long-term survival after local immunotherapy. Tumor GTR before local immunotherapy and relatively weaker immunosuppressive tumor microenvironment are the favorable factors for long-term survival. Larger, controlled studies with standardized treatment protocols, including consistent use of GTR, are warranted to further evaluate the potential benefits of locally delivered immunotherapy. |
| format | Article |
| id | doaj-art-980e2fbfe08c40ec9c6ec693dc5b4a4b |
| institution | DOAJ |
| issn | 1471-2172 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj-art-980e2fbfe08c40ec9c6ec693dc5b4a4b2025-08-20T02:40:14ZengBMCBMC Immunology1471-21722024-12-0125111510.1186/s12865-024-00676-2Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-upHao Duan0Zhenqiang He1Zhenghe Chen2Yukun Chen3Wanming Hu4Ke Sai5Xiangheng Zhang6Jianchuan Xia7Yongqiang Li8Ranyi Liu9Chaowei Zou10Zhongping Chen11Yonggao Mou12Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Biotherapy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Biotherapy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterZhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterDepartment of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer CenterAbstract Purpose Immunotherapy is a promising treatment for cancers but should be optimized for malignant gliomas. Because of immune privilege feature of the brain, local administration of immunotherapy may be a promising strategy for malignant glioma treatment. Identification of patients who may benefit from local immunotherapy is essential. Methods We retrospectively reviewed the clinicopathological characteristics and outcomes of six malignant glioma patients who received local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor resection cavity. Profiles of tumor genome, transcriptome and immune microenvironment were also investigated by genomic target sequencing, RNA sequencing, electrochemiluminescence assay and immunohistochemistry (IHC) staining. Results Four patients died from tumor progression and the overall survival ranged from 10.0 to 33.9 months. Remarkably, two patients, including one diagnosed as diffuse hemispheric glioma H3 G34-mutant (G34-DHG, WHO grade 4) and the other diagnosed as astrocytoma (IDH1 mutation, WHO grade 3) survived more than 20 years without evidence of recurrence. The distinctive clinical feature of the two long-term survivors was tumor gross total resection (GTR) before CIK therapy. NTRK1 mutation was uniquely present and 353 genes were differentially expressed in the long-term survivors compared with the short-term survivors. These differential expression genes were highly associated with immune function. Electrochemiluminescence assay and IHC staining revealed higher expressions of cytokines and lower infiltrations of tumor-associated macrophages in the tumors of the long-term survivors. Conclusion These findings suggest that certain patients diagnosed as malignant gliomas, including G34-DHG (WHO grade 4), can acquire long-term survival after local immunotherapy. Tumor GTR before local immunotherapy and relatively weaker immunosuppressive tumor microenvironment are the favorable factors for long-term survival. Larger, controlled studies with standardized treatment protocols, including consistent use of GTR, are warranted to further evaluate the potential benefits of locally delivered immunotherapy.https://doi.org/10.1186/s12865-024-00676-2GliomaImmunotherapyLong-term survival |
| spellingShingle | Hao Duan Zhenqiang He Zhenghe Chen Yukun Chen Wanming Hu Ke Sai Xiangheng Zhang Jianchuan Xia Yongqiang Li Ranyi Liu Chaowei Zou Zhongping Chen Yonggao Mou Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up BMC Immunology Glioma Immunotherapy Long-term survival |
| title | Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up |
| title_full | Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up |
| title_fullStr | Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up |
| title_full_unstemmed | Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up |
| title_short | Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up |
| title_sort | long term survival after local immunotherapy for malignant gliomas a retrospective study with 20 years follow up |
| topic | Glioma Immunotherapy Long-term survival |
| url | https://doi.org/10.1186/s12865-024-00676-2 |
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