Therapy-induced shaping of the glioblastoma microenvironment: Macrophages at play

Johanna Erbani1, Menno Boon1, Leila Akkari1

  • 1Division of Tumour Biology and Immunology, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.

Insights

Targeting the tumor microenvironment (TME) is crucial for treating glioblastoma. Understanding how tumor-associated macrophages (TAM) and cancer cells interact in specific niches can lead to better combination therapies.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • The tumor microenvironment (TME) significantly influences cancer progression and treatment resistance.
  • Targeting pro-tumorigenic TME components offers a promising strategy to enhance standard-of-care (SOC) treatments for difficult-to-treat cancers like glioblastoma.

Purpose of the Study:

  • To review how distinct glioblastoma TME niches affect therapeutic responses.
  • To explore the interplay between tumor-associated macrophages (TAM) and glioblastoma cells in angiogenic and hypoxic niches.
  • To investigate the co-evolution of these interactions under SOC therapies and their role in disease relapse.

Main Methods:

  • Literature review focusing on glioblastoma TME composition and therapy-induced changes.
  • Analysis of the roles of TAM and glioblastoma cells within specific microenvironmental niches.
  • Examination of therapeutic resistance mechanisms driven by TME alterations.

Main Results:

  • Glioblastoma TME niches, particularly angiogenic and hypoxic ones, critically shape responses to therapy.
  • The dynamic interplay between TAM and glioblastoma cells within these niches fuels malignancy and contributes to therapeutic resistance.
  • SOC therapies can induce significant alterations in the TME, promoting disease relapse.

Conclusions:

  • Understanding therapy-induced TME alterations is essential for identifying novel therapeutic targets.
  • Targeting specific pro-tumorigenic pathways and TAM subsets holds potential for improving glioblastoma treatment outcomes.
  • Developing efficient combination therapies that modulate the TME is a key strategy for enhancing clinical efficacy.

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