# CSF1 Receptor-Mediated Tumor Microenvironment in Lung Cancer

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2022 · —

## Abstract

Thanks to the collaborative efforts of immunologists and oncologists, cancer immunotherapy
and its immunologic research made clinical and scientific breakthrough in treatment of lung
cancer. Here, we assembled an outstanding team of researchers including immunologist,
clinical oncologists, and cancer biologist to investigate the role of tumor-infiltrating myeloid cells
such as macrophages and dendritic cells (DCs), and seek a new approach for myeloid cell-
mediated cancer immunotherapy. Microenvironmental milieu determines the phenotype of
myeloid cells. Our lab reported that Colony Stimulating Factor 1 (CSF1), one of key mediators of
microenvironment, is critical for determining the immunologic function of a DC subset. It has
been well known that tumor cells secrete CSF1 to alter their microenvironment and yet, the
mechanism of action is not fully elucidated. Several agents targeting CSF1 receptor (CSF1R)
are being tested for cancer treatment in ongoing clinical trials. We propose a new role of tumor-
produced CSF1 in altering tumor immune microenvironment toward tumor progression by
producing autotaxin (ATX) which increases the number of protumoral myeloid cells such as
macrophages and DCs. ATX, also known as lysophospholipase D, is secreted extracellularly
and enzymatically generates lysophosphatidic acid (LPA) which is the most abundant
phospholipid in body fluid. LPA is well known to stimulate cellular proliferation, migration and
survival for myeloid lineage cells.
 The proposal is based on the PI’s two new critical discoveries on myeloid cell biology; (1) ATX
is highly expressed in myeloid cells under the control of CSF1 and its receptor (CSF1R)
activation, (2) ATX regulates the size of the residential population of lung myeloid cells in the
CSF1R-dependent manner (CSF1R-ATX pathway). Together these findings have led to the
hypothesis that tumor-produced CSF1 stimulates protumoral myeloid cells to secrete ATX in
order to increase the number of protumoral macrophages and DCs. To validate the hypothesis,
we propose three specific aims. The basic science arm will employ the approaches for proof-of-
concept by utilizing the novel transgenic mice that have the loss or excess of the target genes.
The clinical arm will exploit clinical samples from patients with lung cancer to verify the proof-of-
concept. Lastly, in the translational arm, we will examine the therapeutic potentials of interfering
CSF1R-ATX pathway in the mouse model of lung cancer by adopting state-of-art nano-delivery
system.
By using novel transgenic mice specific to CSF1R-ATX pathway, the clinical materials from
patients and innovative approaches, we will interrogate the CSF1R-ATX pathway in tumor-
infiltrating myeloid cells, which play a key role in tumor cell biology and could lead to the
development of a new therapeutic strategy for lung cancer.

## Key facts

- **NIH application ID:** 10376736
- **Project number:** 5I01BX004981-03
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Gye Young Park
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376736

## Citation

> US National Institutes of Health, RePORTER application 10376736, CSF1 Receptor-Mediated Tumor Microenvironment in Lung Cancer (5I01BX004981-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376736. Licensed CC0.

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