# Inflammatory microenvironment in brain metastasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $318,887

## Abstract

Project Summary/Abstract
Breast cancer brain metastasis (BCBM) has emerged as a dominant clinical problem as treatments for peripheral
disease improve and patients live longer. The blood brain barrier creates a unique challenge as it restricts access
of most standard drugs to brain lesions, so median survival rates have remained stagnant at <2 years. Although
the immune system is a critical controller of metastatic spread in the periphery and the basis for many effective
new therapeutics, little is known about the immune response to BCBM. We have utilized single-cell RNA-
sequencing to investigate the response of microglia, the predominant immune effector in the central nervous
system (CNS), to BCBM. We find that microglia display a dramatic pro-inflammatory response to BCBM,
characterized by increased expression of a diverse array of chemokines and machinery for antigen presentation
through MHCI and MHCII, and that pharmacological depletion of microglia increases metastatic progression. We
will test the hypothesis that microglia play critical roles in suppressing BCBM through 1) chemokine-mediated
peripheral immune recruitment to initiate an inflammatory cascade, and 2) local antigen presentation to sustain
T cell activation in the CNS. This work will establish the basic mechanisms by which microglia control metastatic
outgrowth, how CNS immunity to BCBM develops and ultimately fails, and provide new insights for how to
therapeutically exploit the immune system to control BCBM in patients.

## Key facts

- **NIH application ID:** 10867313
- **Project number:** 5R01CA237376-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Devon A. Lawson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $318,887
- **Award type:** 5
- **Project period:** 2020-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867313

## Citation

> US National Institutes of Health, RePORTER application 10867313, Inflammatory microenvironment in brain metastasis (5R01CA237376-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10867313. Licensed CC0.

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