# Role of Retinoic Acid on Mononuclear Phagocytes in the Sarcoma Microenvironment

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2020 · $15,740

## Abstract

PROJECT SUMMARY
Soft tissue sarcoma (STS) is a rare but heterogeneous collection of fatal malignancies that arise from mesenchymal
tissues. Metastatic STS exhibits a 5-year survival rate of less than 15%, highlighting the need for improved therapies.
Although the clinical success of immunotherapies such as immune checkpoint blockade demonstrates the importance of
the immune system in the control of cancer, the majority of patients fail to respond to these therapies, underscoring the
need to elucidate additional immune evasion mechanisms in solid tumors. It is now known that the abundance of
immunosuppressive myeloid cells such as tumor associated macrophages (TAMs), and conversely, the paucity of
immunostimulatory myeloid cells such as dendritic cells (DCs), pose major barriers to successful anti-tumor immunity.
This proposal builds upon unpublished preliminary data demonstrating that high levels of retinoic acid in the tumor
microenvironment (TME) may be an important immune evasion mechanism utilized by sarcoma. Specifically, retinoic
acid may prevent the intratumoral differentiation of monocytes into DCs. Using sarcoma mouse models, Aim 1.1 explores
the molecular mechanism of retinoic acid's influence on intratumoral monocyte differentiation, and Aim 1.2 explores the
cellular mechanism by which retinoic acid inhibits anti-tumor immunity. As an independent aim, Aim 2 explores the
regulation of retinoic acid production within the TME. Based on unpublished preliminary data demonstrating that Th2
cytokines strongly induce sarcoma cells to produce retinoic acid, Aim 2.1 explores whether IL-13 signaling regulates
retinoic acid production in vivo, and Aim 2.2 seeks to determine the cellular source of IL-13 in sarcoma. Together, this
work will elucidate a novel immune evasion axis in solid tumors and may lead to the development of improved sarcoma
immunotherapies. This project will be co-sponsored by two dedicated mentors with complementary expertise in
immunology and cancer biology. Together, they have assembled a comprehensive training plan that will be instrumental
in the applicant's development into a successful, independent academic investigator.

## Key facts

- **NIH application ID:** 10001325
- **Project number:** 5F30CA236464-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Samirkumar S Devalaraja
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,740
- **Award type:** 5
- **Project period:** 2019-08-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001325

## Citation

> US National Institutes of Health, RePORTER application 10001325, Role of Retinoic Acid on Mononuclear Phagocytes in the Sarcoma Microenvironment (5F30CA236464-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10001325. Licensed CC0.

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