Table 3 Features of the brain tumor microenvironment implicated in radioresistance.

From: Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases

Tumor microenvironment component

Function

Damage-associated molecular patterns (DAMPs)

DAMPs are released from irradiated cells and stimulate macrophages to promote an antitumor immune response. Damage to endothelial cells of the blood-brain may result in radiation necrosis, a late complication of radiotherapy.

Immune cell types

Immune components, including microglia, monocytes, monocyte-derived macrophages, T cells, and MDSCs, are key mediators of treatment response and are responsible for the abscopal effect.

Immune checkpoints

Cancer cells may upregulate immune checkpoints such as PD-L1 and CD47, which represent druggable targets for potential enhancement of radiation response.

Reactive astrocytes

Reactive astrocytes have been shown to promote brain tumor progression and may be activated following radiotherapy.

ROS

ROS are generated by cancer cells as well as stromal cells within the tumor microenvironment following treatment with ionizing radiation, promoting upregulation of hypoxia-inducible factor 1a and mounting of an antioxidant defense. ROS may therefore alter the composition and activity of the tumor microenvironment.

  1. DAMPs damage-associated molecular patterns, HIF-1α hypoxia-inducible factor 1α, MDSCs myeloid-derived suppressor cells, ROS reactive oxygen species.
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