# Disrupting macrophage metabolism to reduce immunosuppression and enhance therapy in pancreatic cancer

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $81,338

## Abstract

Project Summary/Abstract
Pancreatic ductal adenocarcinoma (PDA) has the worst five-year survival rate of any major cancer. The
lethality of PDA is largely due to a lack of effective treatment options. Several barriers in PDA treatment are
conferred by the presence of immunosuppressive myeloid cells, which are highly represented in these tumors.
This immune suppression, driven largely by myeloid cells, renders PDA refractory to immunotherapy which has
proven effective in other solid tumors. Consequently, the elimination or reprogramming of these myeloid cells
offers potential avenues to provide a much-needed breakthrough for the treatment of patients with PDA.
The working hypothesis of this supplemental research proposal is that interruption of the metabolic
mechanisms driving immune suppression will enable T cell killing of PDA cells. This will be examined in two
parts. First, a live cell imaging assay will be developed to assess the requirement of metabolic mechanisms of
immune suppression on the ability of T cells to kill PDA cells in a spatial and temporal manner (Aim 1). Next,
the contribution of proline produced through macrophage catabolism of arginine to collagen produced by
fibroblasts will be measured through a series of assays (Aim 2). Collectively, these data will strengthen the
results from Aim 2 of the parent grant, and promote the diversity of the cancer research community.

## Key facts

- **NIH application ID:** 10499771
- **Project number:** 3R00CA241357-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Christopher J. Halbrook
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $81,338
- **Award type:** 3
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499771

## Citation

> US National Institutes of Health, RePORTER application 10499771, Disrupting macrophage metabolism to reduce immunosuppression and enhance therapy in pancreatic cancer (3R00CA241357-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10499771. Licensed CC0.

---

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