Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma

Michael S. Parappilly, Yuki Chin, Riley M. Whalen, Ashley N. Anderson, Trinity S. Robinson, Luke Strgar, Thomas L. Sutton, Patrick Conley, Christopher Klocke, Summer L. Gibbs, Young Hwan Chang, Guanming Wu, Melissa H. Wong, Alison H. Skalet

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.

Original languageEnglish (US)
Article number4617
Issue number19
StatePublished - Oct 2022


  • cancer biomarker
  • circulating hybrid cells
  • circulating tumor cells
  • uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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