# Targeting the Bone Microenvironment to Reduce Tumor-induced Bone Disease

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Tumor-induced bone disease frequently occurs in patients suffering from some of the most common
malignancies (prostate, breast, lung) in the general population and the Veteran population. While the tumor
microenvironment is known to support tumor growth and bone destruction, the details of these interactions
remain unclear. Despite the well-defined role of bone marrow derived cells in supporting tumor growth and
metastasis in soft tissue sites, surprisingly little is known about their contribution to tumors residing in the bone.
Our group has previously demonstrated that Myeloid Derived Suppressor Cells expand over time as tumors
grow in bone, and our preliminary data show that myeloid cells can infiltrate into tumors residing in bone.
Other groups have suggested that these infiltrating myeloid cells can support tumor growth directly through the
secretion of tumor promoting factors and indirectly by inhibiting the innate immune response, thereby allowing
the tumor to “hide” from immune detection. However, little is known about the immune repressive function of
these cells in bone metastatic disease. Because of the importance of the innate immune response for the
detection of tumors, many groups have begun testing the utility of innate immune activators as a therapy for
reducing tumor in soft tissue, but this has not been explored in TIBD. Our preliminary data show that STING
can stimulate an innate immune response and re-polarize bone marrow derived macrophages to a more
immune-stimulating phenotype, thus suggesting a potential therapeutic approach for shifting the infiltrating
myeloid cells from tumor promoting to tumor inhibiting. We hypothesize that 1) Infiltrating myeloid cells
support tumor growth in bone directly by altering tumor gene expression and by inhibiting anti-tumor
innate immune responses and 2) that innate immune activation via the STING pathway will shift
infiltrating myeloid cells from a pro-tumor to an anti-tumor phenotype that reduces tumor-induced
bone disease. In order to address these hypotheses, we propose to 1) Investigate the function of infiltrating
myeloid cells in promoting tumor growth in bone, 2) Determine if activation of the STING pathway repolarizes
tumor infiltrating myeloid populations towards an antitumor phenotype, and 3) Determine the effect of STING
activation on tumor-induced bone disease. These aims will help further define the role of infiltrating myeloid
cells and determine whether STING activation can reduce these infiltrating cells or reprogram them to induce
an anti-tumor immune response to reduce TIBD.

## Key facts

- **NIH application ID:** 9932275
- **Project number:** 5I01BX001957-08
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Julie A Rhoades (Sterling)
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932275

## Citation

> US National Institutes of Health, RePORTER application 9932275, Targeting the Bone Microenvironment to Reduce Tumor-induced Bone Disease (5I01BX001957-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932275. Licensed CC0.

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