# Reprogramming myeloid cells to inhibit cancer development

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $354,961

## Abstract

Immunosuppressive myeloid cells including myeloid-derived suppressor cells (MDSCs)
contribute to multiple steps of cancer development. A better understanding of the
molecular regulation of the functions of these myeloid cells and the signaling pathways
will support development of novel anti-cancer therapeutic strategies. The leukocyte Ig-like
receptor subfamily B (LILRB) proteins are a group of immune inhibitory receptors with
intracellular immunoreceptor tyrosine-based inhibitory motifs. We have been studying the
roles of these receptors in cancer development and immune regulation. The studies by us
and others suggest that the LILRB family is becoming the next wave of myeloid immune
checkpoint targets for cancer treatment. Here we demonstrated that LILRB3, a myeloid-
specific member of this family, is functionally expressed on human MDSCs, and supports
cancer development in mouse models. Importantly, we identified galectin-4 as an
extracellular protein that binds to LILRB3 and induces LILRB3 activation, and the
intracellular domain of LILRB3 interacts with the adaptor protein TRAF2 to contribute to
NFκB upregulation. Furthermore, we developed anti-LILRB3 blocking antibodies that
efficiently inhibit immunosuppressive activity of human MDSCs in vitro and cancer
development in xenografted humanized mice and in LILRB3-transgenic mice. Our study
suggests that LILRB3 represents an attractive novel target for cancer treatment. Based
on new preliminary results, we propose the following Aims to test the hypothesis that
LILRB3-initiated signaling in immunosuppressive myeloid cells supports cancer
development. In Aim 1, we will determine the function of LILRB3 expressed on myeloid
cells in cancer development. We will then determine whether galectin-4 regulates LILRB3-
mediated signaling in tumor microenvironment to support cancer development in Aim 2.
Finally we will dissect LILRB3 signaling in immunosuppressive myeloid cells in Aim 3. Our
study will elucidate the molecular mechanisms by which LILRB3 regulates the activity of
immunosuppressive myeloid cells, and lead to the development of innovative anti-cancer
strategies based on targeting LILRB3 signaling.

## Key facts

- **NIH application ID:** 10893489
- **Project number:** 5R01CA263079-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** CHENGCHENG ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $354,961
- **Award type:** 5
- **Project period:** 2022-08-22 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893489

## Citation

> US National Institutes of Health, RePORTER application 10893489, Reprogramming myeloid cells to inhibit cancer development (5R01CA263079-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893489. Licensed CC0.

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