# Deconvolution and interruption of the cancer-neuro-immune axis facilitating brain metastases

> **NIH NIH U54** · STANFORD UNIVERSITY · 2023 · $76,446

## Abstract

Black women exhibit a significantly higher incidence and mortality from breast-to-brain
metastasis. This difference in cancer incidence and patient outcomes cannot be solely
explained by cultural and socioeconomic factors necessitating the need to identify
molecular mechanisms governing these differences. Preclinical and clinical studies have
discovered differences in tumor microenvironment (TME) composition and architecture
that are distinct in breast cancers from Black patients. Microvessel density, macrophage
infiltration, and upregulation of immune-related genes have been shown to exist in Black
women compared to White women supporting the idea that ethnic variation can contribute
to distinct changes in the TME. Little is known about the immune environment in breast
cancer brain metastases especially in Black patients. We hypothesize that increased
incidence and progression of breast cancer in Black women is in part due to race-based
differences in tumor-immune interactions. This proposal will examine how the spatial
architecture of the TME reflects distinct tumor-immune interactions, and how these
interactions prime systemic immune tolerance of disseminated tumor cells, enabling
brain-specific metastases.
Stanford Pathology and Neuropathology departments have constructed a tissue
microarray (TMA) containing brain metastases and primary tumors from a diverse group
of breast cancer patients. We will characterize the spatial architecture of these TMAs
using multiplexed ion beam imaging (MIBI). MIBI is a cutting -edge technology that
enables simultaneous quantification of up to 39 proteins in formalin-fixed, paraffin-
embedded tissue samples to create high dimensional tumor-immune maps at subcellular
resolution. Using MIBI, we will construct in-situ subcellular protein spatial maps of both
primary breast cancer and breast cancer brain metastases TME. We will subsequently
identify features of the primary and brain metastases TMEs that are differentially
expressed between Black women and other racial groups. We will focus on identifying
features of the tumor-immune microenvironment (immune composition, spatial
architecture, tumor-immune interactions) that vary based on patient race. The results from
this project will be instrumental in developing appropriate prognostication and targeted
therapies for Black women with breast cancer.

## Key facts

- **NIH application ID:** 10747824
- **Project number:** 3U54CA261717-02S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Melanie Hayden Gephart
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,446
- **Award type:** 3
- **Project period:** 2023-03-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747824

## Citation

> US National Institutes of Health, RePORTER application 10747824, Deconvolution and interruption of the cancer-neuro-immune axis facilitating brain metastases (3U54CA261717-02S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10747824. Licensed CC0.

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