Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is a very rare extranodal non-Hodgkin's lymphoma confined to the brain, eyes, spinal cord, and cerebrospinal fluid (CSF). This disease is highly aggressive. For decades, high-dose methotrexate-based induction regimens have been the standard treatm...

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Main Authors: Lin Zhong MM, Anqing Lu MB, Xiyue Lu MM, Xiaoyin Liu MD, Lujia Cao MM, Shihong Zhu MM, SiJun Diao MM, Xu Cheng MM, Hongwei Wu MB, Jing Chen MD
Format: Article
Language:English
Published: SAGE Publishing 2025-02-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/15330338251319394
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author Lin Zhong MM
Anqing Lu MB
Xiyue Lu MM
Xiaoyin Liu MD
Lujia Cao MM
Shihong Zhu MM
SiJun Diao MM
Xu Cheng MM
Hongwei Wu MB
Jing Chen MD
author_facet Lin Zhong MM
Anqing Lu MB
Xiyue Lu MM
Xiaoyin Liu MD
Lujia Cao MM
Shihong Zhu MM
SiJun Diao MM
Xu Cheng MM
Hongwei Wu MB
Jing Chen MD
author_sort Lin Zhong MM
collection DOAJ
description Primary central nervous system lymphoma (PCNSL) is a very rare extranodal non-Hodgkin's lymphoma confined to the brain, eyes, spinal cord, and cerebrospinal fluid (CSF). This disease is highly aggressive. For decades, high-dose methotrexate-based induction regimens have been the standard treatment for PCNSL and have significantly improved patient overall survival (OS). However, some patients still experience disease recurrence or develop drug resistance. With a deeper understanding of the pathophysiology of PCNSL, various therapies, including CD20 monoclonal antibodies, Bruton's tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, phosphoinositide 3-kinase (PI3 K)/mammalian target of rapamycin(mTOR) inhibitors, and chimeric antigen receptor (CAR) -T cells are increasingly being applied and have demonstrated considerable efficacy. These therapies have paved the way for novel treatment strategies in PCNSL, representing a highly promising field. Investigating the mechanisms, specific targets, and signaling pathways, as well as interactions with the tumor microenvironment (TME), can provide a solid foundation for further exploration and potentially enhance the optimization of treatment approaches for PCNSL. This review seeks to explore the characteristics of the TME in PCNSL, elucidate the molecular mechanisms of various immunotherapies and targeted therapies, examine their interactions with the TME, and summarize the advancements in the research of PCNSL immunotherapy and targeted therapy.
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spelling doaj-art-3efbb928974b496cb6e21a72ed6046ec2025-02-06T11:03:28ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382025-02-012410.1177/15330338251319394Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System LymphomaLin Zhong MM0Anqing Lu MB1Xiyue Lu MM2Xiaoyin Liu MD3Lujia Cao MM4Shihong Zhu MM5SiJun Diao MM6Xu Cheng MM7Hongwei Wu MB8Jing Chen MD9 Department of Hematology, , Chengdu, China Department of Transportation Central, West China Hospital, West China Medical School, Sichuan University/West China School of Nursing, Chengdu, China Department of Anesthesiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China Department of Hematology, , Chengdu, China Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, China Department of Anesthesiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China Department of Hematology, , Chengdu, China Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, ChinaPrimary central nervous system lymphoma (PCNSL) is a very rare extranodal non-Hodgkin's lymphoma confined to the brain, eyes, spinal cord, and cerebrospinal fluid (CSF). This disease is highly aggressive. For decades, high-dose methotrexate-based induction regimens have been the standard treatment for PCNSL and have significantly improved patient overall survival (OS). However, some patients still experience disease recurrence or develop drug resistance. With a deeper understanding of the pathophysiology of PCNSL, various therapies, including CD20 monoclonal antibodies, Bruton's tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, phosphoinositide 3-kinase (PI3 K)/mammalian target of rapamycin(mTOR) inhibitors, and chimeric antigen receptor (CAR) -T cells are increasingly being applied and have demonstrated considerable efficacy. These therapies have paved the way for novel treatment strategies in PCNSL, representing a highly promising field. Investigating the mechanisms, specific targets, and signaling pathways, as well as interactions with the tumor microenvironment (TME), can provide a solid foundation for further exploration and potentially enhance the optimization of treatment approaches for PCNSL. This review seeks to explore the characteristics of the TME in PCNSL, elucidate the molecular mechanisms of various immunotherapies and targeted therapies, examine their interactions with the TME, and summarize the advancements in the research of PCNSL immunotherapy and targeted therapy.https://doi.org/10.1177/15330338251319394
spellingShingle Lin Zhong MM
Anqing Lu MB
Xiyue Lu MM
Xiaoyin Liu MD
Lujia Cao MM
Shihong Zhu MM
SiJun Diao MM
Xu Cheng MM
Hongwei Wu MB
Jing Chen MD
Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
Technology in Cancer Research & Treatment
title Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
title_full Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
title_fullStr Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
title_full_unstemmed Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
title_short Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma
title_sort molecular mechanisms and therapeutic prospects of immunotherapy and targeted therapy in primary central nervous system lymphoma
url https://doi.org/10.1177/15330338251319394
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