# Myeloid cell driven immune suppression in pancreatic cancer

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $36,674

## Abstract

PROJECT SUMMARY
Pancreatic Ductal Adenocarcinoma (PDA) is a deadly disease with a poor five-year survival rate of 10%. PDA is
the most common type of pancreatic cancer and it is characterized by a complex immune suppressive
microenvironment, maintained through the cross-talk between tumor cells, cancer associated fibroblasts (CAFs),
and tumor associated macrophages (TAMs). Myeloid cells are essential for pancreatic cancer tumor growth
and progression. Importantly, the depletion of myeloid cells restores CD8+ T cell mediated anti-tumor immune
responses. Our previous characterization of infiltrating myeloid cells in the neoplastic pancreas has revealed
high levels of Arginase 1 (Arg1) in myeloid cells. Arg1 is an enzyme that depletes the amino acid L-arginine from
the microenvironment and it is a signature marker of alternatively activated and tumor associated macrophages.
Importantly, L-arginine is required for T cell activation. Depletion of L-arginine results in T cell cycle arrest and
inhibition of T cell activation. An increase in Arginase levels has been reported also in other cancers, including
lung, gastrointestinal, and bladder cancer. Thus, Arg1 expression in myeloid cells might be a key mediator of
immune suppression. However, this possibility has not been investigated directly in pancreatic cancer. Based
on these observations, I will test the hypothesis that Arg1 myeloid cells are a key contributor to PDA
immunosuppression and mediate resistance to the anti-PD1 immune checkpoint therapy. To test this
hypothesis, I propose to define the role of myeloid Arg1 in the establishment of immune suppression in PDA
(SA1) and to determine the role of myeloid Arg1 on polarization and metabolic status of macrophages in PDA
(SA2). I will use in vitro and in vivo approaches, including genetically engineered mouse models and
pharmacologic approaches. The objective of this study is to provide novel insights into the role of Arg1 in
pancreatic cancer. This proposal has immediate clinical relevance, since Arg1 inhibitors are currently being
tested in clinical trials. The overall goal is to identify new therapeutic targets for combination therapy in
pancreatic cancer.

## Key facts

- **NIH application ID:** 10151387
- **Project number:** 1F31CA257533-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Rosa Elena Menjivar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,674
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151387

## Citation

> US National Institutes of Health, RePORTER application 10151387, Myeloid cell driven immune suppression in pancreatic cancer (1F31CA257533-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10151387. Licensed CC0.

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