# Dissecting the source and mechanisms of IL-17-mediated modulation of pancreatic tumorigenesis

> **NIH NIH R37** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $370,575

## Abstract

Abstract
The incidence of pancreatic adenocarcinoma (PDAC) is steadily increasing while most treatment modalities
remain ineffective. Therefore, it would not be a surprise to learn that PDAC is one of the top-4 causes of cancer-
related mortality. What is most striking about this malignancy is that even if detected at early stages, outcomes
remain poor. It is well known that pancreatic cancer is characterized by an immunosuppressive environment,
already found surrounding premalignant lesions or pancreatic intraepithelial neoplasia (PanIN), which has been
postulated as one of the main reasons for the lack of response to most therapies. However, the regulatory signals
that precede and support the development of this suppressive TME are not well characterized. The objective of
this grant is to characterize the mechanisms and regulators implicated in the generation of the
immunosuppressive TME that characterizes pancreatic tumorigenic process and to reverse it through
pharmacological and microbial interventions. Our laboratory found that IL-17-secreting immune cells play an
important role in promoting pancreatic tumorigenesis in genetically engineered mouse (GEMM) models of
pancreatic cancer. We now plan to characterize the mechanisms by which IL-17 promotes tumorigenesis by
genetically deleting the IL-17 receptor specifically from the pancreatic oncogenic epithelium using GEMM and
CRISPR/Cas9 (Aim 1). We also found that IL-17 neutralization decreases recruitment of myeloid cells, mostly
neutrophils, and induces CD8+T cells activation and in PDAC orthotopic model. Monoclonal antibodies against
IL-17 or neutrophils will be used to assess the mechanisms employed by IL-17 supporting an
immunosuppressive TME (Aim 2). Finally, we have recently found that fecal microbial transplants can modulate
tumors systemically. In particular, human PDAC-associated gut bacteria is capable of increasing IL-17 levels in
circulation, which may affect distant tumors like pancreatic cancer. We now plan to definitively address the role
gut bacteria in promoting Th17 differentiation and its systemic implications by performing human-into-mice fecal
microbial transplants (Aim 3). Achieving our goals will not only help us better understand immunological as well
as microbial mechanisms implicated in pancreatic tumorigenesis, but will also result in practical novel
interventions with either monoclonal antibodies, narrow spectrum antibiotics or microbial transplants that would
have a direct impact in preventing and/or treating this deadly disease.

## Key facts

- **NIH application ID:** 10051259
- **Project number:** 1R37CA237384-01A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Florencia McAllister
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,575
- **Award type:** 1
- **Project period:** 2020-09-18 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051259

## Citation

> US National Institutes of Health, RePORTER application 10051259, Dissecting the source and mechanisms of IL-17-mediated modulation of pancreatic tumorigenesis (1R37CA237384-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10051259. Licensed CC0.

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