# The role of GPSM3 in tumor-promoting emergency myelopoiesis

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $361,425

## Abstract

Cancer progression is associated with a profound alteration in “emergency” myelopoiesis, leading to
recruitment of mostly immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) and tumor-
associated macrophages (TAM). In response to saturating amounts of tumor-induced colony-stimulating
factors (CSFs), myeloid progenitors divide more frequently to sustain the hematopoietic output necessary
to promote emergency myelopoiesis. Despite the knowledge about the involvement of cytokines and
transcription factors in emergency myelopoiesis, the molecular mechanisms by which the cytokines induce
transcriptional events regulating cancer-driven myelopoiesis remain largely unclear. Our preliminary data show
that G protein signaling modulator-3 (GPSM3) is upregulated selectively in MDSC, either from tumor-
bearing hosts or generated from bone marrow myeloid progenitors by the cytokines G-CSF, GM-CSF and
IL-6. GPSM3-deficient myeloid progenitors display a reduced capacity to differentiate into
granulocytes/monocytes following G-CSF/GM-CSF stimulation. Decreased accumulation of MDSC in
GPSM3-deficient tumor-bearing hosts is linked with an altered expression in the key transcriptional mediators
of myeloid progenitor commitment and differentiation to the granulocytic/monocytic lineage. Moreover, the
immunoregulatory activity of both tumor-induced and cytokine-induced MDSC is dependent on GPSM3.
These results have led to the novel hypothesis that GPSM3 is a master regulator of cancer-associated
myelopoiesis and key driver of the differentiation of MDSCs for both immune suppression and tumor
promotion. In this proposal, we will characterize further the phenotype and function of MDSC in the tumor
microenvironment, and explore the signaling pathways implicated by GPSM3 in regulating MDSC
differentiation and activation using both gain-of-function and loss-of- function approaches.

## Key facts

- **NIH application ID:** 9858274
- **Project number:** 5R01CA208354-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Bin Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,425
- **Award type:** 5
- **Project period:** 2017-03-07 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858274

## Citation

> US National Institutes of Health, RePORTER application 9858274, The role of GPSM3 in tumor-promoting emergency myelopoiesis (5R01CA208354-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858274. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*