New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, an...

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Main Authors: Chuanwei Yang, Xiaohui Ren, Yong Cui, Haihui Jiang, Ming Li, Kefu Yu, Shaoping Shen, Mingxiao Li, Xiaokang Zhang, Xuzhe Zhao, Qinghui Zhu, Xingyao Bu, Song Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1438001/full
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author Chuanwei Yang
Chuanwei Yang
Xiaohui Ren
Xiaohui Ren
Yong Cui
Yong Cui
Haihui Jiang
Ming Li
Ming Li
Kefu Yu
Shaoping Shen
Shaoping Shen
Mingxiao Li
Xiaokang Zhang
Xiaokang Zhang
Xuzhe Zhao
Xuzhe Zhao
Qinghui Zhu
Qinghui Zhu
Xingyao Bu
Song Lin
Song Lin
Song Lin
author_facet Chuanwei Yang
Chuanwei Yang
Xiaohui Ren
Xiaohui Ren
Yong Cui
Yong Cui
Haihui Jiang
Ming Li
Ming Li
Kefu Yu
Shaoping Shen
Shaoping Shen
Mingxiao Li
Xiaokang Zhang
Xiaokang Zhang
Xuzhe Zhao
Xuzhe Zhao
Qinghui Zhu
Qinghui Zhu
Xingyao Bu
Song Lin
Song Lin
Song Lin
author_sort Chuanwei Yang
collection DOAJ
description Primary central nervous system lymphoma (PCNSL) is non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Advances in molecular pathology studies for PCNSL have led to identifying new therapeutic targets and developing novel drugs. New therapeutic strategies, such as creating small molecule targeted agents, immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T (CAR-T) cell therapy, have brought new hope for patients with PCNSL, especially for R/R PCNSL. This review presents recent advances in the treatment of PCNSL, reviews and discusses the efficacy and challenges of targeted therapy and immunotherapy, and provides an outlook on the future development of PCNSL treatment strategies.
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publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-c030830519c84755a6df75d6465e41f42025-08-20T03:01:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14380011438001New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphomaChuanwei Yang0Chuanwei Yang1Xiaohui Ren2Xiaohui Ren3Yong Cui4Yong Cui5Haihui Jiang6Ming Li7Ming Li8Kefu Yu9Shaoping Shen10Shaoping Shen11Mingxiao Li12Xiaokang Zhang13Xiaokang Zhang14Xuzhe Zhao15Xuzhe Zhao16Qinghui Zhu17Qinghui Zhu18Xingyao Bu19Song Lin20Song Lin21Song Lin22Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Peking University Third Hospital, Peking University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaNational Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Institute for Brain Disorders and Beijing Key Laboratory of Brain Tumor, Beijing, ChinaPrimary central nervous system lymphoma (PCNSL) is non-Hodgkin’s lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Advances in molecular pathology studies for PCNSL have led to identifying new therapeutic targets and developing novel drugs. New therapeutic strategies, such as creating small molecule targeted agents, immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T (CAR-T) cell therapy, have brought new hope for patients with PCNSL, especially for R/R PCNSL. This review presents recent advances in the treatment of PCNSL, reviews and discusses the efficacy and challenges of targeted therapy and immunotherapy, and provides an outlook on the future development of PCNSL treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1438001/fullprimary central nervous system lymphomahigh-dose methotrexatetargeted therapyimmunotherapyclinical trial
spellingShingle Chuanwei Yang
Chuanwei Yang
Xiaohui Ren
Xiaohui Ren
Yong Cui
Yong Cui
Haihui Jiang
Ming Li
Ming Li
Kefu Yu
Shaoping Shen
Shaoping Shen
Mingxiao Li
Xiaokang Zhang
Xiaokang Zhang
Xuzhe Zhao
Xuzhe Zhao
Qinghui Zhu
Qinghui Zhu
Xingyao Bu
Song Lin
Song Lin
Song Lin
New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
Frontiers in Immunology
primary central nervous system lymphoma
high-dose methotrexate
targeted therapy
immunotherapy
clinical trial
title New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
title_full New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
title_fullStr New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
title_full_unstemmed New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
title_short New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
title_sort new hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
topic primary central nervous system lymphoma
high-dose methotrexate
targeted therapy
immunotherapy
clinical trial
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1438001/full
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