# The CD93 pathway and melanoma therapy

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $355,706

## Abstract

PROJECT SUMMARY/ABSTRACT
Immune checkpoint blocker therapy has recently greatly improved survival of patients with late- stage
melanoma. However, about 2/3 of patients do not benefit from this therapy. One of main hurdles is that many
melanoma tissues lack effector CD8+ T cells. The immature and dysfunctional blood vessels actively limit T
cell infiltration. Recently vascular normalization has been demonstrated to be able to facilitate effector immune
cell infiltration and to improve cancer immunotherapy. a novel pathway in the
IGFBP7/CD93 interaction, both of which are selectively upregulated in tumor vasculature. Our preliminary
study indicates that disrupting this interaction in vivo normalizes tumor vessels to reduce hypoxia and improve
tumor perfusion in mouse melanoma models. Our examination of tumor tissues reveals that blockade of this
pathway could reinvigorate tumor blood vessels to promote T cell infiltration while limit myeloid-derived
suppressor cells in the tumor. Here we hypothesize that upregulation of this pathway contributes to the tumor
vascular abnormality and targeting this pathway will offer a novel approach to facilitate melanoma
immunotherapy. We will dissect how this pathway is induced in the tumor and consequently leads to tumor
vascular dysfunction and then tumor outgrowth. The mechanisms by which CD93 regulates immune cell
infiltration, as well as its expression causing resistance to anti-PD1 therapy, will be evaluated. By the
completion of these studies, we will gain insight into the biological role of this pathway in the cancer
microenvironment of melanoma and, more importantly, provide a new strategy of promoting immunotherapy in
melanoma.
Our
studies
uncovered

## Key facts

- **NIH application ID:** 10364508
- **Project number:** 1R01CA258302-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Yuwen Zhu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,706
- **Award type:** 1
- **Project period:** 2021-12-03 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364508

## Citation

> US National Institutes of Health, RePORTER application 10364508, The CD93 pathway and melanoma therapy (1R01CA258302-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10364508. Licensed CC0.

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