# Determining the role of myeloid cells in establishing the pre-metastatic niche in pancreatic cancer

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $31,190

## Abstract

PROJECT SUMMARY/ABSTRACT
The most prevalent type of pancreatic cancer, pancreatic ductal adenocarcinoma (PDA) is a lethal cancer which
has not seen substantial progress in survival rate in over four decades. Patients present most often with
metastatic disease, for which there are no effective therapies. The disease is characterized by a complex tumor
microenvironment that consists of fibroblasts and infiltrating immune cells, of a suppressive nature. This
suppressive, cellular cross-talk exists both in the primary tumor and at sites of metastases. It is known that other
cell types, such as immune cells, arrive to these distal sites preceding tumor cell dissemination. These sites are
referred to as the pre-metastatic niche and remodel the distal organs to be favorable for tumor cell colonization
and growth. Recently, immune checkpoint inhibitors have shown success in other cancers, specifically
melanoma, but have shown little success in pancreatic cancer. Our lab, and others, has shown the importance
of myeloid cells in establishing immune suppression at the primary tumor. What remains unknown is how the
pre-metastatic niche is established. My data show that Apolipoprotein E (ApoE) is differentially expressed in the
pre-metastatic niche of tumor-bearing animals. This niche has a robust myeloid population that expresses ApoE,
and is sparsely populated by cytotoxic T cells, indicative of immune suppression at these distal sites. The overall
objective is to understand the cellular interactions that lead to the establishment of the immunosuppressive pre-
metastatic niche in pancreatic cancer. The central hypothesis is that ApoE contribute to the
immunosuppressive nature of the pancreatic cancer microenvironment at the primary and metastatic
sites (Aim 1) and modulates macrophage polarization and function of TAMs, regulating T cell activity
(Aim 2). To test my hypothesis, I will use biomaterial scaffolds to study the pre-metastatic niche in vivo. Scaffolds
are able to recapitulate the pre-metastatic niche and will allow me to characterize the cellular infiltrate and
discover novel targets to block pre-metastatic niche establishment. These experiments will give mechanistic data
on the role of myeloid cells in establishing the pre-metastatic niche in pancreatic cancer.

## Key facts

- **NIH application ID:** 10063306
- **Project number:** 1F31CA247076-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Samantha Blake Kemp
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,190
- **Award type:** 1
- **Project period:** 2020-07-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063306

## Citation

> US National Institutes of Health, RePORTER application 10063306, Determining the role of myeloid cells in establishing the pre-metastatic niche in pancreatic cancer (1F31CA247076-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063306. Licensed CC0.

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