# Function of IL35+ B cells in pancreatic cancer

> **NIH NIH R37** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $446,826

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is notoriously resistant to therapy and has a dismal 5-year survival
rate. Development of PDAC is accompanied by changes in stromal responses and immune surveillance
programs, which are now recognized as major drivers of PDAC tumor evolution and contribute to therapeutic
resistance. We have recently demonstrated that B cells expressing the immunomodulatory cytokine IL35 are
necessary to support the growth of PDAC in murine models. The overarching goals of this proposal are to
elucidate mechanisms underlying the tumor-promoting effect of IL35 expression in B cells, and to investigate the
translational potential of targeting the IL35 pathway as a novel means to augment immunotherapy for this
disease. In Aim 1, we will define essential role for IL35 expressing B cells in establishing an immunosuppressive
microenvironment in PDAC using B cell specific knockout of IL35 and chimeric bone marrow reconstitution. In
Aim 2, we will clarify how B cell receptor (BCR) and CD40 signaling contribute to induction of IL35 expression in
tumor-reactive B cells. To accomplish this task, we will analyze mouse models expressing a fixed BCR with or
without antigen exposure, as well as mouse models lacking CD40 signaling in B cells. We will also perform
signaling pathway analysis in primary B cells and B cell lines. In Aim 3, we will assess the translational potential
of targeting pathogenic B cells in PDAC. Specifically, we will quantify, functionally characterize and study gene
expression signature of IL35+ B cell subset in blood and surgically resected tissues from patients with PDAC.
Additionally, we will evaluate anti-IL35 therapy in combination with immune checkpoint blockade as a novel
therapeutic strategy in syngeneic murine PDAC models. Our proposed research will provide an understanding
of a previously uncharacterized facet of B cell-mediated function in PDAC, use state-of-the-art PDAC murine
models to test strategies that block immune suppressive pathways in TME to enhance the impact of T cell-
reinvigorating therapies, and provide a quantitative and qualitative assessment of IL35+ B cells in human PDAC.
This project will expand our understanding of how IL35 shapes the immunosuppressive tumor microenvironment
and may inform the optimal design of B cell-directed immunotherapy strategies against pancreatic cancer.

## Key facts

- **NIH application ID:** 10112845
- **Project number:** 5R37CA230786-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Yuliya Pylayeva-Gupta
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $446,826
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112845

## Citation

> US National Institutes of Health, RePORTER application 10112845, Function of IL35+ B cells in pancreatic cancer (5R37CA230786-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112845. Licensed CC0.

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