# Immunosurveillance of breast glands with oncogenic germline mutations

> **NIH NIH UG3** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $797,986

## Abstract

Project Summary/Abstract
The overarching goal of the proposed research is to realize the immune system's potential for breast cancer
prevention in BRCA mutation carriers. Immunotherapeutic agents have proven effective in treating metastatic
cancers by reinvigorating the antitumor immune responses that develop during cancer progression and
metastasis. In contrast, our research focuses on cancer immunoprevention and aims to identify the immune
pathways that can prevent breast cancer formation in normal breast glands and block pre-cancerous lesions
from advancing to invasive disease in BRCA mutation carriers. This approach raises a unique opportunity to
discover novel immune mechanisms that can be leveraged for breast cancer prevention and therapy in this high-
risk population. With the ultimate goal of early interception that will eliminate the risk of metastatic disease, we
will investigate the underlying mechanisms of immune cell activation that we have discovered in the BRCA
mutant breast glands. We will (1) determine the breast gland-derived immune factors that induce the immune
response in BRCA mutant breast glands, (2) examine the characteristics of the immune cells infiltrating BRCA
mutation breast glands, (3) investigate the impact of the immune cells in BRCA mutant breast glands on cancer
development, and (4) identify novel interventions that can potentiate antitumor functionality of immune cells in
BRCA mutant breast glands. Importantly, we will leverage our optimized animal models to elucidate critical
immune pathways regulating BRCA mutant breast glands that are difficult to discern in human tissues due to
inter-patient heterogeneity. Ultimately, the proposed research aims to establish the foundation for breast cancer
immunoprevention, benefiting patients at high risk of breast cancer development and recurrence.

## Key facts

- **NIH application ID:** 10877310
- **Project number:** 1UG3CA290300-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shadmehr Demehri
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $797,986
- **Award type:** 1
- **Project period:** 2024-07-05 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877310

## Citation

> US National Institutes of Health, RePORTER application 10877310, Immunosurveillance of breast glands with oncogenic germline mutations (1UG3CA290300-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10877310. Licensed CC0.

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