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Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

Maria B Garcia-Fabiani1,2, Santiago Haase1,2, Andrea Comba1,2

  • 1Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United States.

Frontiers in Oncology
|June 25, 2021
PubMed

Insights

High grade gliomas are aggressive brain tumors with poor prognosis. Immunotherapies show promise but face challenges in clinical translation for glioma patients.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Cancer Biology

Background:

  • High grade gliomas (HGGs) are aggressive brain tumors with limited survival rates (14-17 months) despite standard treatments like surgery and chemo-radiation.
  • There is a critical need for novel therapeutic strategies to improve outcomes for HGG patients.
  • Immunotherapy presents a promising avenue, with encouraging preclinical data, yet clinical translation remains a significant challenge.

Purpose of the Study:

  • To review current understanding of HGGs, their molecular characteristics, and their impact on the tumor immune microenvironment.
  • To discuss the utility and limitations of various murine models in preclinical immunotherapy research for gliomas.
  • To present current immunotherapy strategies in clinical trials and emerging approaches for HGG treatment.

Main Methods:

  • Literature review of HGG biology, immunology, and preclinical models.
  • Analysis of current immunotherapy strategies and clinical trial data for gliomas.
  • Discussion of challenges and future directions in glioma immunotherapy.

Main Results:

  • HGGs possess unique molecular features that influence their immune microenvironment, often creating an immunosuppressive milieu.
  • Preclinical models are crucial but their selection significantly impacts the perceived efficacy of immunotherapies.
  • Despite preclinical promise, immunotherapies have shown limited long-term clinical benefit in glioma patients to date.

Conclusions:

  • Understanding the HGG immune microenvironment is key to developing effective immunotherapies.
  • Careful selection of preclinical models is essential for accurate prediction of clinical outcomes.
  • Further research and novel strategies are required to successfully harness the immune system against incurable gliomas.
Keywords:
clinical trialgliomaimmune microenviromentimmunotherapymouse model

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