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

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $66,390

## Abstract

Project Summary/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 deadly disease.

## Key facts

- **NIH application ID:** 10315610
- **Project number:** 1F32CA265052-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jonathan Robert Weitz
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315610

## Citation

> US National Institutes of Health, RePORTER application 10315610, The role of sympathetic nerve associated macrophages during pancreatic adenocarcinoma progression (1F32CA265052-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10315610. Licensed CC0.

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