# G-CSF inhibition as a colorectal cancer therapy

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $355,323

## Abstract

Project Summary:
Colorectal cancer conveys a high mortality risk as the second most common cause of cancer in the US. While
newer chemotherapy regimens have improved survival, 37% of all patients diagnosed with CRC in the United
States will die of this disease. Clearly, new tumor targets are needed to develop improved treatment
approaches. Harnessing natural anti-tumor immunity is a promising approach to develop new therapies.
develop new therapies. We have found that one potential way to do this is by blocking a critical cytokine that
induces tumor cell proliferation and invasion along with inhibitory immune responses in CRC. Granulocyte
colony-stimulating factor (G-CSF) is a key cytokine present in 88% of human colorectal tumors. Blockade of
this cytokine in a mouse model of colorectal cancer led to activation of protective immune responses and
neoplasm regression. G-CSF may induce regulatory T cell accumulation and potent inhibition of cytotoxic cell
responses. Since these responses may have critical tumor promoting functions, we hypothesize that G-CSF
blockade is protective in CRC by inhibiting tumor progression and inducing anti-tumor immunity. To
test this hypothesis, the following Specific Aims will be completed:
Specific Aim 1: Delineate the role of G-CSF/G-CSFR in colorectal cancer progression and the potential
of blockade as a therapeutic approach. We hypothesize that G-CSF/G-CSFR inhibition will prevent or
regress colorectal cancer metastasis. This will be examined by knocking down G-CSF/G-CSFR in tumor cells,
overexpressing G-CSF/G-CSFR in tumor cells, and employing therapeutic approaches in mouse models of
CRC metastasis. Human CRC tissues will be examined for an association with G-CSF/G-CSFR expression
and metastasis.
Specific Aim 2: Delineate the role of G-CSF/G-CSFR inhibition on enhancing anti-tumor immunity to
protect against CRC progression. We hypothesize that G-CSF induces a tumor immune evasive
microenvironment by inducing immune cell IL-10 production and by inhibiting cytotoxic immune cell responses.
The direct effects of G-CSF on myeloid cell and T cell IL-10 production will be examined. The direct effects of
G-CSF on NK and CD8+ T cells will be examined along with indirect effects through modulation of IL-10 in the
tumor microenvironment will be examined. The ability of G-CSF to inhibit NK cell and CD8+ T cell tumor lytic
function will be assessed. Human CRC and liver metastasis tissues with high vs low G-CSF/G-CSFR
expression will be examined for NK and CD8+ T cell activity.
Thus, for this project, we will examine multiple mechanisms of G-CSF blockade on tumor proliferation and
invasion, activation of protective myeloid and T cell responses, and test blockade of this pathway in an invasive
colorectal cancer model and in human tumor tissues in translational approaches that could lead to a new
treatment for colorectal cancer.

## Key facts

- **NIH application ID:** 10167642
- **Project number:** 5R01CA207051-06
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ellen J. Beswick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,323
- **Award type:** 5
- **Project period:** 2016-07-06 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167642

## Citation

> US National Institutes of Health, RePORTER application 10167642, G-CSF inhibition as a colorectal cancer therapy (5R01CA207051-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10167642. Licensed CC0.

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