# KLRG1 as a novel target for immune checkpoint blockade

> **NIH NIH F31** · BROWN UNIVERSITY · 2020 · $43,410

## Abstract

Project Summary
 Around 90,000 cases of melanoma, the deadliest form of skin cancer, will be diagnosed in the United
States in the coming year. For very early stage melanoma diagnosis, 5-year survival is around 95%. This number
drops to 62% for melanoma that has spread to nearby lymph nodes, and for late stage melanoma the 5-year
survival rate is only 15-20%. Recently, immunotherapy drugs targeting immune cell inhibitory receptors on T
cells have been successfully developed for the treatment of melanoma and a number of other cancers. Many of
these therapies target programmed death-1 (PD-1), an inhibitory receptor that decreases T cell activation. While
most of these therapies focus on T cells, comparably less research has been done on using natural killer (NK)
cells to better combat cancer. NK cells are intriguing targets for immunotherapy for a number of different reasons,
including their cytotoxic abilities and relatively short lifespan. In addition, NK cells have been shown in vivo to
contribute to cancer surveillance. Although great strides have been made in immunotherapy research, many
forms of cancer escape current immunotherapy drugs. Thus, novel therapeutic targets need to be identified for
the development of new treatments. One such target is killer cell lectin-like receptor G1 (KLRG1), which is a well
conserved inhibitory molecule expressed on NK cells. KLRG1 has two main ligands, E-cadherin and N-cadherin.
Engagement of KLRG1 inhibits IFN-γ and TNF-α production and high KLRG1 expression has been correlated
with low proliferative capacity. To determine the role of KLRG1 as a potential NK cell checkpoint, we developed
mice globally deficient for KLRG1 and mice conditionally deficient for KLRG1 in the NK cell lineage and took
advantage of the NK sensitive cancer model, B16. Following B16-E-cadherin administration, we found that
KLRG1 deficient animals had!significantly fewer tumors in the lung tissue, compared to wild type controls. In
addition, compared to the parental B16 cell line, B16-E-cadherin resulted in a higher number of tumors in wild-
type mice. Based on this data, I hypothesize that targeting KLRG1 will unleash the immune cell response to
cancer. In Specific Aim 1, I will determine if targeting KLRG1 on NK cells will reduce tumor development and
progression. In Specific Aim 2, I will determine if simultaneous KLRG1 and PD-1 blockade can synergize to
increase immune cell anti-cancer activity. The findings generated from the proposed work could potentially lead
to the development of new checkpoint inhibitors to treat cancer.
!

## Key facts

- **NIH application ID:** 9969042
- **Project number:** 5F31CA243305-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Angela Tata
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,410
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969042

## Citation

> US National Institutes of Health, RePORTER application 9969042, KLRG1 as a novel target for immune checkpoint blockade (5F31CA243305-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969042. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*