# The frequency and function of Type 3 Innate Lymphoid Cells regulates the melanoma tumor microenvironment

> **NIH NIH F32** · DUKE UNIVERSITY · 2024 · $77,284

## Abstract

Project Summary/Abstract
Malignant tumors escape immune surveillance by evading, suppressing, or distorting immune function. The
recent success of immune checkpoint blockade therapy relies on targeting suppressive mechanisms affecting
effector function of cytotoxic T cells. However, the majority (60%) of patients with advanced melanoma fail to
respond to immune checkpoint inhibitor (ICI) therapy, and many of those that do respond ultimately go on to
develop resistance and disease progression.
While the ability to promote immune responses to tumor has largely focused on tumor specific factors (e.g.
tumor mutational burden), variability in the host immune repertoire may also explain the heterogeneity of
responses seen from ICI treatment failure. ICI therapy works through multiple pathways to release the
immunosuppressive brake on innate and adaptive immune cells. A very important mechanism of action of ICI is
the targeting of inhibitory receptors on CD8+ T cells, which potentiates effector anti-tumor CD8+ T cell function.
Although ICI can renew the effector function of CD8+ T cells, most patients with metastatic melanoma do not
respond to checkpoint blockade due multiple mechanisms spanning both adaptive and innate immunity. A
recently described cell population, innate lymphoid cells (ILCs), are present in secondary lymphoid organs,
peripheral blood, and tissue, and have been described to modulate adaptive immune responses. Type 3 ILCs
(ILC3s) can create immunosuppressive microenvironments through the secretion of Interleukin-17 (IL-17)
leads to the recruitment of immunosuppressive cell populations and creation of an immunosuppressive
microenvironment. ILC3s are the “first responders” to inflammation/tumor and dictate further innate and
adaptive responses that may ultimately determine effectiveness of ICI therapy. However, the role of ILC3s in
the mechanisms behind ICI failure and CD8+ T cell activation is currently not well understood. The ability to
more specifically define the function of ILC3s in the melanoma tumor microenvironment (TME) has the
potential to inform novel combination treatment strategies and dictate the downstream innate and adaptive
cellular responses that drive ICI therapy effectiveness. However, this is currently not well understood.

## Key facts

- **NIH application ID:** 10993053
- **Project number:** 1F32CA294631-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Margaret O'Connor
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,284
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993053

## Citation

> US National Institutes of Health, RePORTER application 10993053, The frequency and function of Type 3 Innate Lymphoid Cells regulates the melanoma tumor microenvironment (1F32CA294631-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10993053. Licensed CC0.

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