Immunotherapy in uveal melanoma: novel strategies and opportunities for personalized treatment

ABSTRACT

Introduction

Uveal melanoma (UM) is the most common intraocular cancer and represents a discrete subtype of melanoma. Metastatic disease, which occurs in half of patients, has a dismal prognosis. Immunotherapy with immune checkpoint inhibitors has produced promising results in cutaneous melanoma but has failed to show analogous efficacy in metastatic UM. This is attributable to UM’s distinct genetics and its complex interaction with the immune system. Hence, more efficacious immunotherapeutic approaches are under investigation.

Areas covered

We discuss those novel immunotherapeutic strategies in clinical and preclinical studies for advanced disease and which are thought to overcome the hurdles set by UM in terms of immune recognition. We also highlight the need to determine predictive markers in relation to these strategies to improve clinical outcomes. We used a simple narrative analysis to summarize the data. The search methodology is located in the Introduction.

Expert opinion

Novel immunotherapeutic strategies focus on transforming immune excluded tumor microenvironment in metastatic UM to T cell inflamed. Preliminary results of approaches such as vaccines, adoptive cell transfer and other novel molecules are encouraging. Factors such as HLA compatibility and expression level of targeted antigens should be considered to optimize personalized management.

KEYWORDS:

• Uveal melanoma
• immunotherapy
• clinical trials
• cancer vaccine
• adoptive cell transfer
• biomarker

Article highlights

• Uveal melanoma represents a molecularly distinct type of melanoma and is further subdivided into molecular subgroups with prognostic significance.

• Only a small subset of UM is immunologically ‘hot’.

• There are important differences in tumor immune microenvironment between primary UM with poor prognosis and hepatic metastases: primary tumor has an inflammatory microenvironment, whereas metastases are immunologically ‘cold’.

• Conventional immune checkpoint inhibition has yielded unremarkable results in metastatic UM.

• Novel immunotherapeutic strategies against metastatic UM include cancer vaccines, adoptive cell transfer, ImmTACs and oncolytic viruses. Their main goal is to reverse immune exclusion in tumor microenvironment, by directing and activating T cells in the tumor sites.

• Very limited data exist in the adjuvant setting, including dendritic cell vaccination and ipilimumab. Adjuvant immune checkpoint treatments are currently the subject of investigation.

• Combinations of conventional immunotherapy with other strategies (HDAC inhibitors, antiangiogenic agents, PARP inhibitors, radiation and liver embolization among others) may boost the former’s efficacy in advanced disease.

• HLA compatibility, expression level of targeted antigens, markers of immune response, as well as the molecular subclassification and mutational burden of UM could serve as predictive biomarkers for these novel immunotherapy strategies.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is affiliated with Roche Diagnostics GmbH. Peer reviewers on this manuscript have no other relevant financial or relationships to disclose

Additional information

Funding

This paper was not funded.