# Role of ADAM12 in regulatory T cell accumulation within T11 claudin-low breast tumors

> **NIH NIH R03** · KANSAS STATE UNIVERSITY · 2020 · $73,840

## Abstract

PROJECT SUMMARY/ABSTRACT
Infiltration of immunosuppressive CD4+CD25+CD127low/-FOXP3+ regulatory T cells (Tregs) into
breast tumors is associated with an invasive phenotype and poor prognosis. Treg accumulation
is particularly prominent in claudin-low breast cancer, an aggressive subtype that is usually
characterized by the triple-negative receptor status. Better understanding of the mechanisms
responsible for Treg accumulation in breast tumors is of the utmost urgency, and the ability to
inhibit intratumoral Treg accumulation and/or activity has an enormous therapeutic potential. The
long-term goal of our research is to elucidate the immunosuppressive mechanisms in breast
tumor microenvironment and to use this knowledge to improve immunotherapies for breast
cancer. The objective of this pilot grant is to test whether ADAM12, a member of the ADAM family
of cell surface metalloproteases, plays a role in immunosuppression using the T11 orthotopic
transplantation mouse model of claudin-low breast cancer. Our central hypothesis is that ADAM12
promotes Treg accumulation in T11 tumors and/or potentiates the suppressive function of tumor-
infiltrating Tregs. To test our hypothesis, we will pursue the following Specific Aims: 1. Determine
the effect of ADAM12 knockout in T11 cells on the number of tumor-infiltrating Tregs in the T11
orthotopic transplantation mouse model of claudin-low cancer. 2. Examine the role of ADAM12 in
regulating the suppressive function of Tregs in T11 claudin-low tumors. Our studies are significant
because they may identify key mechanisms controlling immunosuppression in breast cancer and
lay groundwork for the development of highly selective anti-Treg strategies. The proposed
research is innovative because, for the first time, it will address a possible role of ADAM12, a
breast tumor cell-specific protease, in regulating Treg accumulation and/or function in the tumor
microenvironment.

## Key facts

- **NIH application ID:** 9843649
- **Project number:** 5R03CA235194-02
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Anna Zolkiewska
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,840
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843649

## Citation

> US National Institutes of Health, RePORTER application 9843649, Role of ADAM12 in regulatory T cell accumulation within T11 claudin-low breast tumors (5R03CA235194-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843649. Licensed CC0.

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