# Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $347,558

## Abstract

Project Summary:
 Immune-checkpoint receptors such as CTLA-4 and PD-1 have been successfully targeted for
cancer immunotherapy. Our earlier work has identified V domain Immunoglobulin Suppressor of
T cell Activation (VISTA) as an immune-checkpoint protein that critically regulates anti-tumor
immunity. Despite this progress, how VISTA inhibits T cell activation is not understood. Our
current study has identified a novel VISTA-interacting receptor that is expressed on murine and
human T cells and mediates the suppressive effect of VISTA. The overarching goals of this
proposal are to define the cellular and molecular mechanisms of this novel T cell coinhibitory
complex. Specific aim 1 will dissect the interactions between VISTA and its receptor and establish
the relevance of ubiquitin-modifying enzymes to the inhibitory signaling. Aim 2 will examine the
role of VISTA and its receptor in regulating tumor-specific T cell responses, utilizing a newly
generated conditional knockout mice and novel inhibitors that block this inhibitory receptor
complex. The protein expression level of VISTA and its receptor in human cancer tissues will also
be examined. Together, these proposed studies will build a foundation for developing novel
inhibitors that target the VISTA receptor complex for cancer immunotherapy.

## Key facts

- **NIH application ID:** 9974483
- **Project number:** 5R01CA164225-08
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Li Lily Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,558
- **Award type:** 5
- **Project period:** 2012-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974483

## Citation

> US National Institutes of Health, RePORTER application 9974483, Vista, A Novel Checkpoint that Suppresses Anti-Tumor T Cell Responses (5R01CA164225-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974483. Licensed CC0.

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