# Targeting Liver-X-Receptor Regulation of Prostate Cancer Immune-Evasion

> **NIH NIH R21** · SAINT LOUIS UNIVERSITY · 2021 · $177,066

## Abstract

Project Summary: Metastatic prostate cancer will claim the lives of over 30,000 men this year alone.
There are no effective treatments that prevents disease progression. In prostate cancer, lipid production
is known to drive tumor growth throughout the early and late stages. In addition to providing building
blocks for tumor cell replication, lipids produced by tumors have been shown to repress immune activity,
which allows tumors to grow unchecked. Clinically used immunotherapies which deactivate built-in anti-
inflammatory pathways called immune checkpoints, have been highly effective at harnessing the tumor-
killing abilities of immune cells. Unfortunately checkpoint blockade inhibitors are notoriously ineffective
at treating metastatic prostate cancer. Studies have shown that tumors produce lipid metabolites,
endogenous ligands of Liver-X-Receptor (LXR) that activate and suppress the function of immune cells.
In line with this shutting down production of lipid metabolites in tumor cells reverses tumor suppression
resulting in tumor destruction. As prostate cancer cells rely heavily on lipid synthesis, we postulated
that prostate tumors produce LXR ligands to suppress immune function. Our studies have highlighted
that prostate tumors produce lipids that activate LXR and suppress the activity of helper and effector
T-cells as well as dendritic cells, all key cell types that direct a robust anti-tumor immune response. We
theorized that prostate tumors specifically produce high activity LXR ligands and by suppressing LXR
activity in immune cells we could stimulate tumor destruction. In this proposal, we will explore this
hypothesis using three specific aims. We propose firstly to identify if prostate tumors produce unique
lipids, LXR ligands, that are especially effective at suppressing immune cell activity. We also intend to
determine if the concentrations of specific tumor lipids correlate with disease severity or responsiveness
to treatment. Secondly, we will test if drugs which suppress LXR activation, can stimulate destruction
of prostate tumors when used alone and probe whether these drugs can sensitize prostate tumors to
checkpoint immunotherapies. Lastly, we will determine how LXR signaling regulates immune cell
metabolism and the manner in which immune cells respond to prostate tumor growth. These studies
should lead to the development of a novel dual activity immunotherapy for prostate cancer that has
intrinsic cytotoxicity and immune stimulatory activity.

## Key facts

- **NIH application ID:** 10137199
- **Project number:** 5R21CA249341-02
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Ian Mitchelle Sayo de Vera
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $177,066
- **Award type:** 5
- **Project period:** 2020-04-02 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137199

## Citation

> US National Institutes of Health, RePORTER application 10137199, Targeting Liver-X-Receptor Regulation of Prostate Cancer Immune-Evasion (5R21CA249341-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137199. Licensed CC0.

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