Circulating Melanoma Cell Numbers Correlate with TIGIT-Positive Cytotoxic T Cell Counts in Advanced-Stage Melanoma Patients

Cells. 2023 Mar 9;12(6):856. doi: 10.3390/cells12060856.

Abstract

Despite the rising public awareness of the risk factors and the possible prevention of melanoma development, it remains challenging in terms of diagnosis and treatment. To improve the clinical situation of patients, it would be especially beneficial to develop prognostic methods for the effective and continuous assessment of the disease course. The solution could lie in the selection of effective biomarkers derived from the tumor microenvironment, increasing the effectiveness of melanoma prognoses and monitoring. Hence, in this study, we evaluated the number of circulating melanoma cells (CMCs) in representative blood samples of melanoma patients vs. healthy controls, as well as the proportion of particular cytotoxic T cells in the total lymphocyte and leukocyte population as a reflection of immune resistance. The results were correlated with the clinical parameters of the patients to examine the potential value of CMC quantification and lymphoid cell phenotyping in melanoma diagnostics, prognostics, and treatment outcome monitoring. The CMC numbers were significantly higher in melanoma patients than in healthy controls. However, an analysis of the correlations between the baseline CMC counts and the clinical parameters found no significant results. In turn, we found significant differences between the groups in the percentage of various profiles of CD8+ cytotoxic T lymphocytes characterized by TIGIT and TIM-3 differential expression. Importantly, the CMC number correlated with CD8+TIGIT+ and CD8+TIGIT+TIM-3- cytotoxic T cell counts in the melanoma patient group. Considering the above, the combination of CMCs and the immunological status of the patient, as defined by the prevalence of selected immune cell types, seems to be a promising approach in melanoma diagnostics and prognostics.

Keywords: circulating melanoma cells; cytotoxic T cells; diagnosis; immune checkpoints; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Leukocyte Count
  • Melanoma* / pathology
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes, Cytotoxic* / metabolism
  • Tumor Microenvironment

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • Receptors, Immunologic
  • TIGIT protein, human

Grants and funding

The research was funded by the National Science Centre (Poland) MINIATURA grant, No. 2020/04/X/NZ5/01314.