# The dynamic myeloid-enriched microenvironment of glioblastoma: a major challenge to immunotherapy efficacy

## TL;DR

This review discusses how the complex tumor environment in glioblastoma limits immunotherapy success and highlights the need for better models and personalized treatments.

## Contribution

The paper provides a comprehensive overview of factors shaping the glioblastoma microenvironment and emphasizes the need for integrative models to improve immunotherapy.

## Key findings

- The glioblastoma tumor microenvironment strongly influences immunotherapy outcomes.
- Factors like tumor mutations, treatments, and patient characteristics modulate the microenvironment.
- Integrative models are needed to better study and target the glioblastoma microenvironment.

## Abstract

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, and current treatments remain poorly efficient. In this context, immunotherapies may represent promising strategies. However, their efficacy is often limited by a strong negative impact of the tumor microenvironment (TME) of glioblastoma. Several factors such as tumor cells mutational profile, previous lines of conventional treatments, or biological factors, have been shown as involved in TME modulation. In this review, our goal is to give an overview of the main modulating factors of the TME of glioblastoma tumors. We will also highlight the importance of developing complex and integrative models to study this microenvironment. At the end, by highlighting critical components of the glioblastoma microenvironment, this review aims to support the development of next-generation, more effective and personalized immunotherapeutic strategies.

Created in BioRender. Lamorlette, C. (2026) https://BioRender.com/0j9owwq.Flowchart illustrating interactions in glioblastoma (GBM) environment. Initial cancerization undergoes mutational burden affecting tumor heterogeneity and immunogenicity. GBM standard treatments, including surgery, corticosteroids, chemotherapy, and radiotherapy, as well as patient gender, influence the microenvironment. Surface and secretory phenotypes also modulate immune and cerebrovascular cells in the GBM microenvironment. Recruitment occurs from peripheral to neurovascular compartments. Adapting treatments to the microenvironment improves therapeutic success, and GBM patients management.

Created in BioRender. Lamorlette, C. (2026) https://BioRender.com/0j9owwq.