# Dissecting the roles of a novel immune-checkpoint receptor complex in driving T cell dysfunction in cancers

> **NIH NIH F31** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $40,090

## Abstract

Project Summary.
 Immune checkpoint inhibitors (ICI) have become the breakthrough therapy in the era of
cancer immunotherapy. However, one of the major challenges is that the majority of patients do
not respond, indicating the urgent need to identify and target non-redundant immuno-suppressive
pathways. In this regard, our preliminary studies have identified a novel cross talk mechanism
between two immune checkpoint proteins, namely V-domain Immunoglobulin Suppressor of T-
cell Activation (VISTA) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT). We
hypothesize that VISTA and TIGIT form a novel co-inhibitory receptor complex that dampens T
cell activation and drives T cell dysfunction. This proposal will test this hypothesis by two specific
aims: First, we will perform mutagenesis studies and subject these mutants to binding and
functional studies to better understand the binding epitopes and the causal link between binding
and function. Lastly, we will investigate how VISTA and TIGIT drive T cell dysfunction during
tumor growth in both a polyclonal and antigen specific manner. Together, these studies will
warrant future studies to develop therapeutic inhibitors that block this IC receptor complex,
reverse T cell dysfunction, and improve clinical outcomes in human cancers.

## Key facts

- **NIH application ID:** 10315469
- **Project number:** 1F31CA257276-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Cassandra Gilmour
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,090
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315469

## Citation

> US National Institutes of Health, RePORTER application 10315469, Dissecting the roles of a novel immune-checkpoint receptor complex in driving T cell dysfunction in cancers (1F31CA257276-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315469. Licensed CC0.

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