# Systematic interrogation of the pancreatic cancer microenvironment in patient-derived specimens

> **NIH NIH U01** · DANA-FARBER CANCER INST · 2020 · $611,615

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of only 8%. Despite
success in other cancer types, immunotherapy approaches in PDAC have not shown efficacy. PDAC
demonstrates a heterogeneous and immunosuppressive tumor microenvironment (TME) that is poorly
understood and serves as a barrier to effective immunotherapy strategies in this disease. We propose that an
improved understanding of the TME and novel approaches that target key tumor-stroma interactions will
enable remodeling of the immunosuppressive TME to enhance the efficacy of current and future
immunotherapy strategies. In particular, we believe that successful combination immunotherapy approaches in
PDAC will include strategies that alter myeloid cells to relieve immunosuppression, cytotoxic therapies that
target tumor cells to improve immune response, and agents that augment anti-tumor T cell activity. In this
project, we will perform a comprehensive characterization of the PDAC TME in both primary and metastatic
PDAC in the baseline untreated context as well as across multiple different clinical therapies. In Aim 1, we will
utilize single-cell transcriptomic and proteomic technologies to provide a cellular atlas of the PDAC TME at
unprecedented resolution. In Aim 2, we will examine how the PDAC TME changes with chemotherapy,
radiation therapy and a novel CCR2 inhibitor that modulates macrophage recruitment in the TME. For these
studies, we will utilize human samples derived from both resectable and metastatic patients on clinical trials at
Dana-Farber Cancer Institute. We will employ a novel ex vivo co-culture approach to enable rapid functional
evaluation of tumor-stroma interactions and how they may impact immunotherapy responses. Lastly, in Aim 3
we will employ faithful immune competent PDAC mouse models and a novel cytokine delivery platform to
investigate how targeted cytokine delivery to the TME may alter myeloid cell recruitment and function and
improve immune responses. We have assembled a multi-disciplinary collaborative team including experts in
PDAC biology and genetics, immunologists and translational oncologists to comprehensively study PDAC TME
and identify novel opportunities to develop combination immunotherapy approaches in this devastating
disease.

## Key facts

- **NIH application ID:** 10242454
- **Project number:** 4U01CA224146-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** William C. Hahn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,615
- **Award type:** 4N
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242454

## Citation

> US National Institutes of Health, RePORTER application 10242454, Systematic interrogation of the pancreatic cancer microenvironment in patient-derived specimens (4U01CA224146-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10242454. Licensed CC0.

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