# Pancreatic Cancer Development: Genetic and Immune Regulation

> **NIH NIH P01** · STANFORD UNIVERSITY · 2021 · $2,129,462

## Abstract

Abstract (Overall):
Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease whose mechanisms of development remain
incompletely understood. Evidence suggests that pancreatic cancers may arise from acinar cells undergoing a
process called acinar to ductal metaplasia (ADM) or from ductal cells to give rise to Pancreatic Intraepithelial
Neoplasias (PanINs). How mutations or combinations of mutations promote PDAC development and the role of
inflammation in the process still remains unclear. Moreover, interactions between immune cells, cancer-
associated fibroblasts (CAFs) and cancer cells can promote PDAC development and progression, but much
remains to be learned about how signaling between cells in the tumor microenvironment (TME) affects the stem
cell compartment (`stemness') thought to underlie PDAC development and promotes immune evasion. Thus,
multiple questions about fundamental mechanisms governing PDAC development persist.
To address these challenges, our superb and highly interactive team will identify genetic and stromal (immune
cells and CAFs) interactions and pathways that regulate the inception and progression of PDAC using innovative
mouse models and human tissue-based approaches. We propose three Projects to address the following overall
aims:
1. Identify the originating cell(s) and deconstruct genetic pathways underlying PDAC initiation
2. Discover immune signals that cross-talk with epithelial cells and CAFs to promote pancreas cancer
development and stemness
3. Investigate the impact of tumor genetics on PDAC immunobiology and response to macrophage-targeted
immunotherapy
Effort on these projects will be organized through an Administrative and Biostatistics Core (A) and empowered
by two Research Cores, focused on human tissue procurement (Core B), and use of high-dimensional imaging
to measure cell and signaling interactions in tissues (CODEX; Core C).
The participating investigators on this P01 lead teams that have collaborated productively for years and have
generated compelling preliminary data that support the potential for unraveling the genetic and immune signaling
mechanisms underlying PDAC development, and developing new immunotherapeutic strategies for PDAC,
which has proven frustratingly resistant to immuno-based therapies.
Our studies should broadly impact pancreas cancer biology and importantly, elucidate the reciprocal interactions
between immune and non-immune compartments (epithelial, CAFs) in shaping the tumor microenvironment
during disease evolution. accelerate discovery of novel diagnostic or preventive strategies for early-stage
disease, or therapeutics for advanced PDAC.

## Key facts

- **NIH application ID:** 10187124
- **Project number:** 1P01CA244114-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** LAURA D ATTARDI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,129,462
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187124

## Citation

> US National Institutes of Health, RePORTER application 10187124, Pancreatic Cancer Development: Genetic and Immune Regulation (1P01CA244114-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187124. Licensed CC0.

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