Abstract
Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch® CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch®. Specifically, the percentage of patients with ≥2 CMCs was significantly higher using S100-EPISPOT than CellSearch® (48% and 21%, respectively; p = 0.0114). Concerning CMC prognostic value, only the CellSearch® results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.
Highlights
Melanoma is the most malignant skin cancer, and its incidence rate is increasing worldwide.Early stage and localized melanoma can be cured by surgical resection
To develop a new EPithelial ImmunoSPOT (EPISPOT) assay for Circulating melanoma cells (CMCs) detection, two different melanoma cell lines
To develop a new EPISPOT assay for CMC detection, two different melanoma cell lines (WMand MV3), derived from metastatic sites, were used
Summary
Melanoma is the most malignant skin cancer, and its incidence rate is increasing worldwide.Early stage and localized melanoma can be cured by surgical resection. Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival (OS) (six to nine months). Melanoma management has recently undergone revolutionary changes with the discovery of predictive tumor biomarkers (BRAF mutations and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4)) and the development of the associated treatments. These new treatments, alone or in combination, have dramatically improved the outcome of patients with metastatic melanoma. The anti-PD-1 drug pembrolizumab has demonstrated benefits to progression-free survival (34–38%) and objective responses (21–25%) at six months compared with chemotherapy
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