Improving Immunotherapy for Uveal Melanoma
Research type
Research Study
Full title
Characterising the spatial and temporal evolution of the uveal melanoma immune microenvironment to identify mechanisms of resistance, and opportunities for immunotherapeutics
IRAS ID
373370
Contact name
Omar Fakih
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
3 years, 6 months, 1 days
Research summary
This study focuses on Uveal melanoma (UM), the most common eye cancer. Although most patients can have treatment to the eye, in about half of patients it will come back, or metastasise, mostly to the liver, after which it is universally fatal. Unlike its counterpart, skin melanoma, which responds well to immunotherapy called checkpoint inhibitors (ICIs), metastatic UM shows limited benefit from ICIs, highlighting the need for alternative treatment approaches.
Tebentafusp is a novel immunotherapy that has been a major step forward for UM patients, and is the first treatment that improves their survival, now becoming a standard of care for eligible patients. It works by redirecting immune T-cells to attack cancer cells that express a target protein, gp100. Other emerging immunotherapies, like a cancer-targeting modified virus called RP-2, have also shown early promise. However, many patients are ineligible for tebentafusp, and even for those eligible, most will develop treatment resistance and ultimately succumb to the disease.
Resistance to ICIs and tebentafusp may be linked to tumour cells reducing the expression of antigens, or target proteins, on their cell surface, and the presence of immunosuppressive cell types in the tumour's micro-environment (TME). Key questions remain in how the TME influences patients’ outcomes and treatment responses.
We will investigate the biological and immune characteristics of UM as it progresses from the eye to the liver, and following treatment, using matched samples from patients with metastatic UM in combination with advanced scientific techniques that will allow us to understand genetic, protein, and structural changes as well as cellular relationships in the TME. By identifying markers of response and resistance, we aim to inform the development of more effective treatment strategies. We also expect our findings to have broader relevance to other cancers that metastasise to the liver, and respond poorly to immunotherapy.REC name
Wales REC 5
REC reference
26/WA/0188
Date of REC Opinion
3 Jul 2026
REC opinion
Favourable Opinion