# Do Tumor-Immune Interactions Prime Systemic Tolerance of Triple-Negative Breast Cancer Brain Metastases?

> **NIH NIH K99** · STANFORD UNIVERSITY · 2021 · $162,617

## Abstract

PROJECT ABSTRACT/SUMMARY
It is widely estimated that 90% of cancer-related deaths are caused by metastasis. This statistic underscores our inability
to manage cancer once it disseminates through the body, and our need to better understand the molecular
mechanisms that drive metastasis. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that occurs in
10-20% of cases. Taken as a group, TNBCs pose an unmet clinical challenge in many ways: (1) TNBCs represents the
most aggressive and most metastatic subtype of breast cancer, (2) up to 46% of late-stage TNBC patients will develop
brain metastases, (3) TNBC patients are at four-times higher risk of developing diffuse metastases on the surface of the
brain (leptomeningeal disease), which is rapidly and universally fatal, and 4) women of African ancestry have an up to
80% higher likelihood of developing TNBC – making TNBC a cancer disparity. Previous studies demonstrate that
primary TNBC is highly immunogenic, and immune infiltration is associated with improved prognosis. However, little is
known about the immune environment in TNBC brain metastases and how tumor-immune interactions effect
metastatic potential. Recognizing these pressing issues, I have chosen to focus my career as an independent cancer
researcher on using a systems biology approach to uncover molecular mechanisms that underlie metastasis and race-
specific cancer disparities. A comprehensive mentoring, research, and career development plan will be executed
over the course of the K99 and R00 training period, which will provide me with the necessary tools to make an
early transition to independence. First, to visualize tumor-immune interactions, I will construct an in-situ protein map of
TNBC brain metastases using MIBI – a cutting-edge multiplexed imaging method (AIM 1). I will use a validated imaging
analysis pipeline to quantitate the composition and spatial architecture of the tumor-immune microenvironment and
determine the extent to which these features correlate with patient outcomes. In AIM 2, I will identify tumor-immune
receptor-ligand pairs using single-cell RNA-sequencing on TNBC brain metastases samples. Lastly, in AIM 3, I will use
MIBI to visualize tumor-immune interactions in primary TNBCs to determine whether interactions in the primary tumor
microenvironment prime immune system tolerance of disseminated tumor cells enabling brain metastases. I will validate
relevant targets by measuring their expression in patient cerebral spinal fluid (CSF), which contains brain-tumor-
associated cell-free RNA. The results of my proposed postdoctoral research will positively impact public health as
they will reveal key tumor-immune interactions responsible for priming the immune system for metastasis, and
will generate the first “TNBC brain metastasis interactome”. My results will lead to the discovery of new molecular
targets with the primary goal of reducing metastasis-driven cancer mortality. The K99 career development...

## Key facts

- **NIH application ID:** 10115537
- **Project number:** 1K99CA256522-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Maxine Umeh Garcia
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,617
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115537

## Citation

> US National Institutes of Health, RePORTER application 10115537, Do Tumor-Immune Interactions Prime Systemic Tolerance of Triple-Negative Breast Cancer Brain Metastases? (1K99CA256522-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115537. Licensed CC0.

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