# Regulation of mRNA homeostasis by PD-L1

> **NIH NIH R16** · ST. JOHN'S UNIVERSITY · 2024 · $164,000

## Abstract

Abstract
The goal of this project is to identify mechanisms by which immune checkpoint programmed death
ligand 1 (PD-L1) regulates mRNA homeostasis of anti-apoptotic genes. As a cell surface protein,
PD-L1 inhibits T cell responses, resulting in immune escape. However, PD-L1 also has important
non-immune intracellular functions that are much less understood. Our recent studies show that IFNγ
induces the nuclear translocation and accumulation of PD-L1 in ovarian and prostate cancer cells.
In addition, our preliminary data indicate that suppression of the IFNγ-induced PD-L1 expression
increases apoptosis and decreases mRNA levels of NFκB-dependent anti-apoptotic genes. Based
on those findings, we will test the central hypothesis that the intracellular PD-L1 serves as a
regulator of anti-apoptotic gene mRNA homeostasis. In Aim 1, we will determine whether PD-L1
increases the levels of anti-apoptotic genes by promoting their transcription, and/or whether it
increases stability of their mRNAs in ovarian and prostate cancer cells. In Aim 2, we will determine
whether PD-L1 directly binds to the anti-apoptotic gene promoters and facilitates their acetylation,
and we will investigate whether PD-L1 binds the anti-apoptotic mRNAs and affects their subcellular
localization. Although the project focuses on the NFκB-dependent anti-apoptotic genes, the results
will likely reveal general mechanisms by which PD-L1 regulates synthesis and/or stability of other
mRNAs. Immunotherapies targeting cell surface PD-L1 have shown impressive clinical outcomes in
many cancers; however, only a fraction of patients achieves durable responses, highlighting our
incomplete understanding of the mechanisms of PD-L1 functions. Findings from this study will
provide the first data on the mechanisms of how PD-L1 regulates mRNA homeostasis of anti-
apoptotic genes. This information will advance our understanding of the intracellular, immune-
independent functions of PD-L1, and may lead to the development of novel therapies that target PD-
L1 anti-apoptotic functions in cancer cells. In addition, this R16 SuRE project will enhance the
research environment at St. John’s University by providing students from underrepresented
backgrounds with numerous opportunities to learn the fundamentals of biomedical research.

## Key facts

- **NIH application ID:** 10842267
- **Project number:** 5R16GM149263-02
- **Recipient organization:** ST. JOHN'S UNIVERSITY
- **Principal Investigator:** Ivana Vancurova
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2023-05-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842267

## Citation

> US National Institutes of Health, RePORTER application 10842267, Regulation of mRNA homeostasis by PD-L1 (5R16GM149263-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10842267. Licensed CC0.

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