Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment
The preclinical and clinical development of novel immunotherapies for the treatment of central nervous system (CNS) tumors is advancing at a rapid pace. High-grade gliomas (HGG) are aggressive tumors with poor prognoses in both adult and pediatric patients, and innovative and effective therapies are...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.966458/full |
| _version_ | 1811269752363941888 |
|---|---|
| author | Andrea Franson Brandon L. McClellan Brandon L. McClellan Brandon L. McClellan Maria Luisa Varela Andrea Comba Mohammad Faisal Syed Kaushik Banerjee Ziwen Zhu Nazareno Gonzalez Marianela Candolfi Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Maria Graciela Castro Maria Graciela Castro Maria Graciela Castro |
| author_facet | Andrea Franson Brandon L. McClellan Brandon L. McClellan Brandon L. McClellan Maria Luisa Varela Andrea Comba Mohammad Faisal Syed Kaushik Banerjee Ziwen Zhu Nazareno Gonzalez Marianela Candolfi Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Maria Graciela Castro Maria Graciela Castro Maria Graciela Castro |
| author_sort | Andrea Franson |
| collection | DOAJ |
| description | The preclinical and clinical development of novel immunotherapies for the treatment of central nervous system (CNS) tumors is advancing at a rapid pace. High-grade gliomas (HGG) are aggressive tumors with poor prognoses in both adult and pediatric patients, and innovative and effective therapies are greatly needed. The use of cytotoxic chemotherapies has marginally improved survival in some HGG patient populations. Although several challenges exist for the successful development of immunotherapies for CNS tumors, recent insights into the genetic alterations that define the pathogenesis of HGG and their direct effects on the tumor microenvironment (TME) may allow for a more refined and targeted therapeutic approach. This review will focus on the TME in HGG, the genetic drivers frequently found in these tumors and their effect on the TME, the development of immunotherapy for HGG, and the practical challenges in clinical trials employing immunotherapy for HGG. Herein, we will discuss broadly the TME and immunotherapy development in HGG, with a specific focus on glioblastoma multiforme (GBM) as well as additional discussion in the context of the pediatric HGG diagnoses of diffuse midline glioma (DMG) and diffuse hemispheric glioma (DHG). |
| first_indexed | 2024-04-12T21:47:39Z |
| format | Article |
| id | doaj.art-aa190e5206994038b0c0a18dd0e91df3 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-12T21:47:39Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-aa190e5206994038b0c0a18dd0e91df32022-12-22T03:15:34ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-09-01910.3389/fmed.2022.966458966458Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironmentAndrea Franson0Brandon L. McClellan1Brandon L. McClellan2Brandon L. McClellan3Maria Luisa Varela4Andrea Comba5Mohammad Faisal Syed6Kaushik Banerjee7Ziwen Zhu8Nazareno Gonzalez9Marianela Candolfi10Pedro Lowenstein11Pedro Lowenstein12Pedro Lowenstein13Pedro Lowenstein14Maria Graciela Castro15Maria Graciela Castro16Maria Graciela Castro17Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesImmunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesInstituto de Investigaciones Biomédicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, MI, United StatesBiosciences Initiative in Brain Cancer, Biointerface Institute, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesBiosciences Initiative in Brain Cancer, Biointerface Institute, University of Michigan, Ann Arbor, MI, United StatesThe preclinical and clinical development of novel immunotherapies for the treatment of central nervous system (CNS) tumors is advancing at a rapid pace. High-grade gliomas (HGG) are aggressive tumors with poor prognoses in both adult and pediatric patients, and innovative and effective therapies are greatly needed. The use of cytotoxic chemotherapies has marginally improved survival in some HGG patient populations. Although several challenges exist for the successful development of immunotherapies for CNS tumors, recent insights into the genetic alterations that define the pathogenesis of HGG and their direct effects on the tumor microenvironment (TME) may allow for a more refined and targeted therapeutic approach. This review will focus on the TME in HGG, the genetic drivers frequently found in these tumors and their effect on the TME, the development of immunotherapy for HGG, and the practical challenges in clinical trials employing immunotherapy for HGG. Herein, we will discuss broadly the TME and immunotherapy development in HGG, with a specific focus on glioblastoma multiforme (GBM) as well as additional discussion in the context of the pediatric HGG diagnoses of diffuse midline glioma (DMG) and diffuse hemispheric glioma (DHG).https://www.frontiersin.org/articles/10.3389/fmed.2022.966458/fullgliomasimmunotherapytumor microenvironmentgene therapyimmune suppression |
| spellingShingle | Andrea Franson Brandon L. McClellan Brandon L. McClellan Brandon L. McClellan Maria Luisa Varela Andrea Comba Mohammad Faisal Syed Kaushik Banerjee Ziwen Zhu Nazareno Gonzalez Marianela Candolfi Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Pedro Lowenstein Maria Graciela Castro Maria Graciela Castro Maria Graciela Castro Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment Frontiers in Medicine gliomas immunotherapy tumor microenvironment gene therapy immune suppression |
| title | Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment |
| title_full | Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment |
| title_fullStr | Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment |
| title_full_unstemmed | Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment |
| title_short | Development of immunotherapy for high-grade gliomas: Overcoming the immunosuppressive tumor microenvironment |
| title_sort | development of immunotherapy for high grade gliomas overcoming the immunosuppressive tumor microenvironment |
| topic | gliomas immunotherapy tumor microenvironment gene therapy immune suppression |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.966458/full |
| work_keys_str_mv | AT andreafranson developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT brandonlmcclellan developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT brandonlmcclellan developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT brandonlmcclellan developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT marialuisavarela developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT andreacomba developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT mohammadfaisalsyed developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT kaushikbanerjee developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT ziwenzhu developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT nazarenogonzalez developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT marianelacandolfi developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT pedrolowenstein developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT pedrolowenstein developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT pedrolowenstein developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT pedrolowenstein developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT mariagracielacastro developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT mariagracielacastro developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment AT mariagracielacastro developmentofimmunotherapyforhighgradegliomasovercomingtheimmunosuppressivetumormicroenvironment |