# Only the strong survive: therapeutic selective pressure drives medulloblastoma leptomeningeal metastasis

## TL;DR

Radiation therapy for medulloblastoma can cause inflammation and spread of cancer to the leptomeninges, but dexamethasone can reduce this effect.

## Contribution

The study reveals that radiation-induced inflammation and blood-brain barrier breakdown drive metastasis, and dexamethasone can mitigate this process.

## Key findings

- Radiation therapy increases myeloid cell infiltration and cytokine levels, promoting leptomeningeal metastasis.
- Dexamethasone cotreatment reduces cytokines and preserves blood-brain barrier integrity, limiting metastasis.
- Targeting inflammation can decrease the overall disease burden in medulloblastoma patients.

## Abstract

Medulloblastoma (MB) is the most common malignant tumor in the central nervous system in childhood and regularly metastasizes to the leptomeninges following radiation therapy. Using patient‐derived medulloblastoma models and genetically engineered mouse models, Nör et al. observed enhanced inflammation and infiltration of myeloid cells within the brain following irradiation. The authors identified inflammatory cytokines and the resulting breakdown of blood–brain barriers as the main culprits of MB leptomeningeal metastasis. This study demonstrated that targeting inflammation through the use of dexamethasone effectively reduced systemic inflammatory cytokines and the resulting radiation‐induced leptomeningeal metastasis.

Radiation therapy induces cancer cell death and immune cell infiltration, mainly monocytes, macrophages, and dendritic cells. Elevated serum cytokine levels and disruption of the blood–brain barrier promote leptomeningeal dissemination. Cotreatment with dexamethasone reduces cytokine levels, preserves barrier integrity, and limits metastatic spread, resulting in decreased overall disease burden.