Immunoprofiling of Primary Uveal Melanoma
Research type
Research Study
Full title
Characterisation of the primary uveal melanoma immune microenvironment and its influence on outcome: a comprehensive multi-modality approach.
IRAS ID
247220
Contact name
Sarah, E Coupland
Contact email
Sponsor organisation
University of Liverpool
Clinicaltrials.gov Identifier
Professor Sarah Coupland_PG_20180131_021, Fight For Sight Grant Application
Duration of Study in the UK
3 years, 4 months, 5 days
Research summary
Research Summary
Uveal melanoma (UM) is the most common primary eye cancer in adults. In approximately half of all patients, the cancer cells will spread from the eye via the bloodstream to distant sites, usually to the liver. Once UM cells have established their secondary ‘colonies’ in the liver, current therapies are not effective. One treatment that has shown efficacy in other types of cancer is immunotherapy. Immunotherapy aims to boost the body's natural defences to attack and eliminate the cancer cells, which appear to have developed mechanisms to escape detection. To date, there is limited evidence of benefit for immunotherapy in the treatment of metastatic UM, compounded by a lack of knowledge of the immune microenvironment that would allow for the development of the most appropriate treatments. To fully exploit this approach for UM, this study aims to provide a deeper understanding of the different types and function of immune cells present in the primary cancer. To achieve this, we will use “state-of-the-art” techniques that are able to: (1) recognise and isolate immune cells from the individual tumours to tell us the number and type of immune cells present; (2) provide a picture of the location of the immune cells in relation to the cancer cells; and (3) identify markers on the surface of the cancer and immune cells that may be used to activate an immune response. All analyses will be performed on eye and blood samples gifted by consenting UM patients, to the Ocular Oncology Biobank, at the University of Liverpool. By creating a comprehensive overview of the ‘immune landscape’ in UM, we will be able to determine how this relates to specific tumour characteristics, and uncover ways to enhance the ability of the immune system to fight the cancer cells.
Summary of Results
By identifying and characterising immune cells present in primary uveal melanoma, a rare eye cancer, we can begin to understand how the immune microenvironment contributes to tumour development and progression, immune tolerance and resistance to immune therapies. In this study we examined the immune profile of primary uveal melanoma and demonstrated that loss of a protein associated with an increased risk of tumour spread, BAP1, is correlated with upregulation of several genes associated with suppressive immune responses, including HLA‐DR, CD38, and CD74. Single‐cell analysis of primary UM by mass cytometry confirmed the expression of these and other markers revealing important functions of infiltrating immune cells in UM, most being regulatory CD8+ T lymphocytes and tumour‐associated macrophages. These findings aid the understanding of how the immune response is organised in BAP1 negative uveal melanoma, which will further enable the development of focused immunotherapy approaches.
REC name
London - Queen Square Research Ethics Committee
REC reference
18/LO/1027
Date of REC Opinion
5 Jun 2018
REC opinion
Favourable Opinion