# Boosting Antitumor Immunity by Blocking Both Tumor and Adipose DDR1

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2020 · $476,885

## Abstract

ABSTRACT
 Despite significant clinical breakthroughs in anticancer immunotherapy, the efficacy of current
immunotherapies in breast cancer is modest. Only a small fraction of breast cancer patients have a clinical
response; complete responses to these agents are exceedingly rare. The underlying mechanisms of tissue-
specific immune regulation in breast cancer remains to be elucidated. Furthermore, how comorbidities such as
obesity influence antitumor immunity in breast cancer is even less understood.
 Discoidin domain receptor 1 (DDR1) is a collagen receptor with an intrinsic tyrosine kinase activity. High
DDR1 expression in breast cancer is associated with poor patient outcomes and attenuated antitumor
immunity. We found complex tumor-promoting actions for both tumor and adipose DDR1 in the breast tumor
microenvironment. Tumor DDR1 suppresses antitumor immunity, whereas adipose DDR1 is required for diet-
induced obesity, tumor-promoting cytokine production, and immune modulation. Our preliminary data further
indicate that the shed extracellular domain of DDR1 alone is sufficient for its functions in tumor and adipose
cells, which has not previously been reported. We therefore hypothesize that DDR1 in the breast tumor
microenvironment promotes tumor progression by dampening antitumor immunity, enabling adiposity, and
abetting immune-adipose cell-tumor crosstalk. We predict that blocking kinase-independent DDR1 signals can
boost antitumor immunity and response to anticancer immunotherapies, especially in patients with obesity. To
test this hypothesis, in this R01 application, we will determine how tumor DDR1 suppresses antitumor
immunity (Aim 1), how adipose DDR1 contributes to obesity-associated cancer progression (Aim 2), and how
DDR1 carries out its immune-suppressive functions independent of its kinase activity (Aim 3). With combined
expertise in cancer biology, tumor immunology, and clinical oncology, our multidisciplinary team is well
positioned to validate our novel hypothesis.
 The fact that DDR1 has distinct functions in different cell compartments of the breast tumor
microenvironment underscores the complexity of tumor-stromal interactions. By investigating tumor and
adipose DDR1 in an integrative and comprehensive manner as proposed here, we will fill major gaps of
knowledge about tumor-initiated immune suppression and obesity-associated comorbid effects. Given the
adipocyte-rich tumor microenvironment in breast cancer and the growing numbers of patients with obesity and
breast cancer, our proposed studies address an unmet clinical need and promise to inform the development of
new strategies to enhance antitumor immunity for breast cancer patients, especially for those with obesity.
 !

## Key facts

- **NIH application ID:** 9980667
- **Project number:** 1R01CA246707-01A1
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Rong Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $476,885
- **Award type:** 1
- **Project period:** 2020-05-05 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980667

## Citation

> US National Institutes of Health, RePORTER application 9980667, Boosting Antitumor Immunity by Blocking Both Tumor and Adipose DDR1 (1R01CA246707-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980667. Licensed CC0.

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