# The role of sympathetic nerve associated macrophages during pancreatic adenocarcinoma progression

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $2,500

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all major cancers. While
immunotherapy has revolutionized treatment for numerous cancers, such treatments for patients with
pancreatic ductal adenocarcinoma (PDAC) have not been successful. Failure of the current immunotherapeutic
approaches are due to numerous features of pancreatic tumors including; poor immunogenicity and a highly
immunosuppressive tumor microenvironment (TME). Macrophages are considered as a focal point for
interventional studies during PDAC given that they regulate immunosuppression, promote a pro-fibrotic
microenvironment, as well as play an essential role in promoting tumor progression along local nerves. The
autonomic nervous system work in close partnership with local macrophages. Autonomic nerves stimulate
cytokine and chemokine production in macrophages that contribute to their aforementioned functions,
however, the signaling mechanisms by which nerves communicate with the immune system and coordinate the
release of tumorigenic factors are unknown. Based on our preliminary data, I hypothesize that noradrenaline
(NA) released from sympathetic nerves binds to adrenergic receptors on sympathetic nerve associated
macrophages (SAMs), which consequently support tumor progression. To study the communication between
local pancreatic nerves and immune cells, we are using ex vivo pancreatic tissue slices from human and
mouse PDAC tumors. With this technological platform, we are able to visualize nerves, macrophages, and
tumor cells with minimal disruption from their natural state. We will characterize [Ca2+]i responses in
macrophages in response to autonomic neurotransmitters, as well as use a targeted in-vivo approach in order
to determine if blocking adrenergic signaling within immune cells promotes anti-tumor responses. Combined
with our preliminary physiological data, we will use molecular approaches to further explore this crosstalk. We
expect our results to identify communication networks between macrophages, tumor cells and autonomic
nerves in the setting of PDAC perineural invasion that will prompt new therapeutic approaches for this dedaly
disease.

## Key facts

- **NIH application ID:** 10973789
- **Project number:** 3F32CA265052-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jonathan Robert Weitz
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2023-11-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973789

## Citation

> US National Institutes of Health, RePORTER application 10973789, The role of sympathetic nerve associated macrophages during pancreatic adenocarcinoma progression (3F32CA265052-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10973789. Licensed CC0.

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