# The Roles of a Novel Immune-Checkpoint Receptor Complex in Driving T Cell Dysfunction in Cancer

> **NIH NIH R21** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $188,169

## Abstract

Summary
 Immune checkpoint inhibitors (ICI) have become the breakthrough therapy in the era of
cancer immunotherapy. However, one of the major challenges is that majority of patients do not
respond, indicating the urgent need to identify and target non-redundant immunosuppressive
pathways. Our preliminary studies have identified a novel cross-talk mechanism between two
immune checkpoint receptors. We hypothesize that this novel cross-talk mechanism drives T cell
exhaustion and impair anti-tumor immune response. We will test this hypothesis by two specific
aims: in Aim 1, we will determine the causal relationship between receptor binding and the
inhibitory effects on T cell activation. In Aim 2, we will investigate how this novel cross-talk
mechanism drives T cell exhaustion and whether blocking this axis can enhance T cell-mediated
anti-tumor immunity. Together, these studies will guide future studies to target this novel axis,
reverse T cell exhaustion, and improve clinical outcomes in cancer patients.

## Key facts

- **NIH application ID:** 10435225
- **Project number:** 1R21CA258618-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Li Lily Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $188,169
- **Award type:** 1
- **Project period:** 2022-02-08 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435225

## Citation

> US National Institutes of Health, RePORTER application 10435225, The Roles of a Novel Immune-Checkpoint Receptor Complex in Driving T Cell Dysfunction in Cancer (1R21CA258618-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10435225. Licensed CC0.

---

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