# Disrupting the immune and drug-privileged microenvironment in pancreas cancer

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $602,955

## Abstract

PROJECT SUMMARY
Pancreatic ductal adenocarcinomas (PDA) develop an intense fibroinflammatory infiltrate that helps promote
disease progression and therapeutic resistance. Recent progress has identified essential barriers in this
complex microenvironment that impede drug delivery and suppress immunity. These processes include the
prohibitive interstitial pressures generated by high concentrations of hyaluronan (HA) complexed with water,
dense fibrosis associated with fibrillar collagen deposition, and multiple classes of immunosuppressive and
pro-tumorigenic cells such as myeloid-derived suppressor cells and macrophages. The team assembled in this
project has made many of the seminal discoveries described above. In addition, we have developed several
highly novel and powerful experimental platforms to rigorously interrogate the complex mechanisms and
interactions among various compartments in the tumor microenvironment that collectively conspire to promote
the survival of pancreas cancers and metastases and thwart treatment. Our overarching hypothesis is that
significantly improving survival for PDA patients will require targeting not only the tumor epithelial cell, but also
the three compartments that support its oncogenesis: hematopoietic, mesenchymal and extracellular matrix. In
the following, we propose to investigate the combination of cytotoxic therapy with stromal disruption and
myeloid cell modulations to maximize engagement of anti-tumor immunity and treatment efficacy. We will
pursue these investigations in four distinct experimental platforms that offer complementary strengths and
mitigate limitations: 1) genetically engineered mouse models (GEMM) of autochthonous PDA; 2) syngeneic
allografts; 3) patient-derived xenograft (PDX) systems; and 4) patient-derived organoids (PDO).

## Key facts

- **NIH application ID:** 10242457
- **Project number:** 4U01CA224193-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Sunil R Hingorani
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $602,955
- **Award type:** 4N
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242457

## Citation

> US National Institutes of Health, RePORTER application 10242457, Disrupting the immune and drug-privileged microenvironment in pancreas cancer (4U01CA224193-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242457. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*