# Targeting the Immunosuppressive Tumor Microenvironment in Pancreatic Cancer

> **NIH NIH R50** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $66,191

## Abstract

Project Summary
Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest human malignancies, and little progress
towards its treatment has been achieved over the past several decades. The tumor microenvironment as a
whole has been believed to be immunosuppressive. However, how different cell populations within the stroma
contribute to the establishment of the immunosuppression is not fully understood. Immunotherapy has so far
produced disappointing results in pancreatic cancer. A potential challenge is the redundancy of immune
suppressive pathways in this disease. Thus, a thorough understanding of the biology of this disease is
necessary to optimize our approaches to treatment and identify opportunities for combination therapy and
prevent potential feedback mechanisms that result in tumor resistance and relapse. The research program of
Unit Director Dr. Marina Pasca di Magliano's laboratory addresses the interaction between pancreatic cancer
cells and components of the stroma, with the long-term goal to identify new therapeutic targets. We previously
showed that ablating tumor-infiltrating myeloid cells, including tumor associated macrophages (TAMs) and
myeloid derived suppressor cells, can restore anti-tumor immune response. In order to translate these results
to clinically applicable strategies, we need to identify and target the signals that mediate the cross-talk between
tumor cells and their microenvironment and that are responsible for immune suppression. As a research
Investigator in Pasca di Magliano laboratory, I am actively pursuing two areas of research on immune
regulation and fibroblasts function in pancreatic cancer. 1) I have been leading research on understanding the
cross-talk between tumor cells, immune cell infiltrates and fibroblasts in the pancreatic cancer
microenvironment. Within this wider project, I am focusing on identifying the signals that mediate the
establishment of an immune suppressive microenvironment, in particular mechanisms involved in TAM
polarization and TAM induced immune suppression, as well as investigating therapeutic modulation of the
epithelial-myeloid crosstalk to improve immune checkpoint therapy in pancreatic cancer; 2) I have been
contributing to project aimed at understanding fibroblast heterogeneity within pancreatic cancer, and define the
origins of functions of different fibroblast subsets during the onset and progression of pancreatic cancer. My
contribution also includes training of graduate and undergraduate students. I am invested in the training of
junior personnel in the laboratory, and I manage collaborations with other groups. I seek to work as a team
member, with primary responsibility on individual projects and a supporting role on other projects to ensure the
success of Unit Director's research program.

## Key facts

- **NIH application ID:** 10479792
- **Project number:** 5R50CA232985-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yaqing Zhang
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $66,191
- **Award type:** 5
- **Project period:** 2018-09-13 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479792

## Citation

> US National Institutes of Health, RePORTER application 10479792, Targeting the Immunosuppressive Tumor Microenvironment in Pancreatic Cancer (5R50CA232985-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10479792. Licensed CC0.

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