Applying Single-Cell Technology in Uveal Melanomas: Current Trends and Perspectives for Improving Uveal Melanoma Metastasis Surveillance and Tumor Profiling

Abstract

Uveal melanoma (UM) is the most common primary adult intraocular malignancy. This rare but devastating cancer causes vision loss and confers a poor survival rate due to distant metastases. Identifying clinical and molecular features that portend a metastatic risk is an important part of UM workup and prognostication. Current UM prognostication tools are based on determining the tumor size, gene expression profile, and chromosomal rearrangements. Although we can predict the risk of metastasis fairly accurately, we cannot obtain preclinical evidence of metastasis or identify biomarkers that might form the basis of targeted therapy. These gaps in UM research might be addressed by single-cell research. Indeed, single-cell technologies are being increasingly used to identify circulating tumor cells and profile transcriptomic signatures in single, drug-resistant tumor cells. Such advances have led to the identification of suitable biomarkers for targeted treatment. Here, we review the approaches used in cutaneous melanomas and other cancers to isolate single cells and profile them at the transcriptomic and/or genomic level. We discuss how these approaches might enhance our current approach to UM management and review the emerging data from single-cell analyses in UM.

Heterogeneity and molecular landscape of melanoma: implications for targeted therapy

“…The efficacy of metastatic UM research is substantially hindered by the constraints imposed by small sample sizes, which severely diminish the study's statistical power. Moreover, the accessibility of single-cell tools remains limited across various institutions and countries [195,252,253].…”

“…Nonetheless, emerging evidence indicates that analyzing CTCs and circulating free DNA, particularly in high-risk UM patients, could enhance mUM surveillance. Indeed, employing single-cell analysis to explore the tumor cell microenvironment and CTCs has already yielded fresh insights into UM tumor biology [239,252,253].…”

“…Indeed, the growing adoption of single-cell technologies facilitates the detection of circulating tumor cells and the characterization of transcriptomic profiles in individual, drug-resistant tumor cells. These advancements have facilitated the identification of viable biomarkers conducive to targeted therapeutic interventions [4,20,174,253,254].…”

“…One such challenge arises from the limitations inherent in neoantigen prediction algorithms, which may fail to accurately identify subtle signals of immunoediting within data characterized by inherent noise. Addressing this issue necessitates the utilization of single-cell analysis to comprehensively capture and analyze these nuanced alterations [174,253].…”

Resistance to immune checkpoint therapies by tumour-induced T-cell desertification and exclusion: key mechanisms, prognostication and new therapeutic opportunities

“…New microfluidic techniques have been developed to detect sensitive molecular changes in response to ICT [ 82 ]. For example, researchers have developed the single-cell DEPArray platform that performs automated isolation of rare immune infiltrated cells from intraocular and liver biopsies of primary and metastatic UM, respectively, [ 83 , 84 ]. This platform is expected to address the clinical needs for single-cell based precision immune prognostication in the clinical setting in the near future.…”