# Epithelium-derived alarmins role in breast cancer immunoprevention

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $801,869

## Abstract

Project Summary/Abstract:
Advances in cancer immunology has led to the successful use of patients' own immune cells to combat
metastatic cancers. However, the therapeutic potential of the immune system in eliminating premalignant cells
and preventing their progression to invasive cancers is unclear. To determine the benefit of activating the
immune system to prevent cancer development and recurrence, we study the immune pathways that lead to
effective immune activation against early phases of breast cancer development. Breast cancer is the most
common internal cancer and second cause of cancer deaths among women in the United States. Importantly,
the individuals at high risk of developing breast cancer due to underlying genetic mutations and those with
premalignant lesions can be clinically identified and treated. Therefore, discovering an effective approach to
activate the patients' own immune system against early breast precursor lesions may yield a lasting memory
that can prevent breast cancer development and recurrence in this high-risk population. Our previous studies
have demonstrated that a skin-derived immune factor called thymic stromal lymphopoietin (TSLP) suppresses
the early stages of skin and breast cancer development. We have been able to extend these finding to clinics
through a randomized double-blind clinical trial in which we find TSLP induction to promote a robust immune
activation against skin cancer precursors and their complete clearance. In order to determine the precise
mechanism of TSLP-induced immune response against early premalignant cells in the breast, and to extend
our findings to other similar immune factors in high-risk patients, we aim to (1) determine the immune cells and
signals that target breast premalignant cells in response to TSLP, (2) investigate the role of other immune
factors released by breast cells that can induce immune response to block breast cancer development, and (3)
determine the factors that are driving the immune response in the breast glands of patients with genetic
mutations and utilize them for induction of an optimal immune response against early breast cancer. The
outcomes of the proposed research will establish a foundation for the use of the immune system in blocking
breast cancer development and provide novel therapeutic targets for breast cancer immunoprevention.

## Key facts

- **NIH application ID:** 10234167
- **Project number:** 5U01CA233097-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shadmehr Demehri
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $801,869
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234167

## Citation

> US National Institutes of Health, RePORTER application 10234167, Epithelium-derived alarmins role in breast cancer immunoprevention (5U01CA233097-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10234167. Licensed CC0.

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