# Immune microenvironment in brain metastais

> **NIH CA R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2026 · $554,732

## Abstract

Project Summary/Abstract
Brain metastasis is a lethal disease and major clinical unmet need for breast cancer patients. There is growing
interest in immunotherapies to treat central nervous system (CNS) cancers, but greater understanding of the
unique immune microenvironment of the brain is needed to develop effective treatment strategies. The brain
contains a unique type of tissue resident macrophage called microglia that constitute 10-15% of brain cells and
play diverse functions in CNS homeostasis and disease. In recent work, we found that microglia are central
regulators of the anti-tumor T cell response and are critical to suppress brain metastasis (Evans et al., Nature
Cell Biology, 2023). In this renewal proposal application, we will investigate three key gaps in knowledge raised
during this work: 1) how do microglia promote the T cell response? Although microglia are principally known
as phagocytes, but we observe a robust upregulation of antigen presentation machinery in response to brain
metastasis. In Aim 1, we will test the hypothesis that microglia promote the T cell response primarily through
local antigen presentation in the CNS and that they are main source of this function. 2) Why does disease
continue to progress in many animals despite a robust immune response? In Aim 2, we will test the
hypothesis that our observed accumulation of Tregs is a main mechanism for disease progression through direct
suppression of microglia in the CNS. 3) How do microglia initially become activated in response to brain
metastasis? We observe that they rapidly sense and home to sites of infiltrating cancer cells. In Aim 3, we will
test the hypothesis that the purinergic receptor P2RY12 that mediates chemotaxis in other brain disease settings
is essential for microglia activation and chemotaxis to metastasis. Each of these phases of the microglia
response – their initial activation, their regulation of adaptive immunity, and their potential suppression in
advanced metas

## Key facts

- **NIH application ID:** 11298534
- **Project number:** 2R01CA237376-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Devon A. Lawson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $554,732
- **Award type:** 2
- **Project period:** 2026-05-08T00:00:00 → 2031-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11298534

## Citation

> US National Institutes of Health, RePORTER application 11298534, Immune microenvironment in brain metastais (2R01CA237376-06A1). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11298534. Licensed CC0.

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