# Fibroblast orchestration of the immune response in pancreatic cancer

> **NIH NIH U01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $786,440

## Abstract

Pancreatic cancer is a deadly malignancy, direly in need of new therapeutic approaches. Pancreatic cancer is
characterized by extensive accumulation of a fibroinflammatory stroma, containing abundant fibroblasts. Long
believed to be a uniform cell population, fibroblasts have emerged as a heterogeneous and functionally important
component of the tumor. Yet, the literature on fibroblasts in pancreatic cancer is controversial, with studies
supporting both a pro- and an anti-tumor role. Our preliminary data show that oncogenic KRAS, a hallmark
mutation of pancreatic cancer, expressed in tumor cells extrinsically reprograms the transcriptional program of
fibroblasts. Further, continuous expression of epithelial oncogenic Kras is required to maintain expression of a
panel of inflammatory cytokines in fibroblasts. Unlike mouse tumors, human pancreatic cancer is highly
heterogeneous in terms of genetic alterations and histological characteristics of cancer cells. How fibroblasts are
reprogrammed in the context of different types of human pancreatic cancer and how they contribute to
carcinogenesis is unclear. Lastly, most in depth studies on pancreatic cancer are based on largely White patient
populations, while the disease is equally prevalent in all race groups. The University of Michigan/Henry Ford
Health System team together has access to a large patient volume, diverse patient populations (with 30% HFHS
patients being African American), and the skillset to characterize and functionally assess fibroblasts on
pancreatic cancer. We will map fibroblast heterogeneity across tumors in a diverse patient population. We will
evaluate whether fibroblast heterogeneity correlates with different subtypes of tumor cells (classified as classical
and mesenchymal). We will further take advantage of the genetically engineered mouse models available in our
group to target fibroblast reprogramming at different stages of carcinogenesis. Overall, our work will shed light
on the regulation and function of pancreatic CAFs and open the way for new therapeutic approaches targeting
this population.

## Key facts

- **NIH application ID:** 10925247
- **Project number:** 5U01CA274154-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Howard C. Crawford
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $786,440
- **Award type:** 5
- **Project period:** 2022-09-19 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925247

## Citation

> US National Institutes of Health, RePORTER application 10925247, Fibroblast orchestration of the immune response in pancreatic cancer (5U01CA274154-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10925247. Licensed CC0.

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