# Type I Interferon Regulation of PD-L1 Expression and Function in MDSCs

> **NIH VA I01** · CHARLIE NORWOOD VA MEDICAL CENTER · 2020 · —

## Abstract

Project Abstract
 Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells
(IMCs). Under physiological conditions, IMCs quickly differentiate into mature granulocytes, macrophages or
dendritic cells. By contrast, under pathological conditions, a partial block of IMC differentiation into mature
myeloid cells results in the expansion and activation of this population. In human cancer patients, massive
accumulation of MDSCs is a hallmark of cancer progression. One key function of MDSCs is to inhibit activation of
cytotoxic T lymphocytes (CTLs) through multiple suppressive mechanisms. PD-L1 has emerged as a new
immune suppressive factor of MDSCs. However, the function of MDSC-expressed PD-L1 in suppression of CTL
activation in the tumor microenvironment is currently controversial. Our preliminary studies determined for the
first time that type I IFNs regulate constitutive PD-L1 expression in MDSCs in an autocrine manner. We further
determined that IFNAR1 controls PD-L1 expression level in MDSCs in the tumor microenvironment. Therefore,
type I IFNs might play a dominant role over IFNγ in up-regulating PD-L1 expression in MDSCs in the tumor
microenvironment, which remains to be determined. Our central hypothesis is that type I IFNs regulate PD-L1
expression in tumor-infiltrating MDSCs and both tumor-expressed and MDSC-expressed PD-L1 contributes to
CTL suppression and tumor immune evasion in human colon cancer. The objectives are: 1) elucidate the
molecular mechanism underlying PD-L1 expression regulation by type I IFNs in MDSCs; 2) Determine the
relative contributions of tumor-expressed and MDSC-expressed PD-L1 in suppression of CTL activation and
tumor immune evasion; and 3) Test the hypothesis that type I IFN regulates PD-L1 expression in MDSCs in
human colon cancer patients. Successful completion of the proposed studies will determine the function of
MDSC-expressed PD-L1 in immune suppression and tumor immune evasion in human colorectal cancer patients
and identify novel molecular target to enhance the efficacy of checkpoint inhibitor immunotherapy in human colon
cancer.

## Key facts

- **NIH application ID:** 9850858
- **Project number:** 5I01CX001364-02
- **Recipient organization:** CHARLIE NORWOOD VA MEDICAL CENTER
- **Principal Investigator:** KEBIN LIU
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850858

## Citation

> US National Institutes of Health, RePORTER application 9850858, Type I Interferon Regulation of PD-L1 Expression and Function in MDSCs (5I01CX001364-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850858. Licensed CC0.

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