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Updated: Oct 3, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint
Fernanda Costa Svedman1,2, Marie Jalsenius2, Veronica Höiom1,2
1Department of Oncology and Pathology, Karolinska Institutet, 171-77 Stockholm, Sweden.
Abstract:
Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Methods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients' baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20-1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08-3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25-4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease.
Insights
High plasma thymidine kinase activity (TKa) indicates poorer outcomes for melanoma patients treated with immune checkpoint inhibitors (ICI). This novel biomarker warrants further investigation for prognostic and predictive roles in melanoma.
Area of Science:
- Oncology
- Biomarkers
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICI) show variable efficacy in disseminated melanoma.
- Thymidine kinase (TK) is involved in DNA synthesis and repair.
- This study investigates plasma TK activity (TKa) as a novel biomarker in melanoma.
Purpose of the Study:
- To analyze plasma TKa levels as a potential biomarker in metastatic cutaneous melanoma patients treated with ICI.
- To correlate TKa levels with baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Plasma samples collected pre-treatment from 90 unresectable metastatic cutaneous melanoma patients receiving ICI (anti-CTLA-4 and/or anti-PD-1).
- Plasma TKa levels measured using the DiviTum TKa ELISA assay.
- Statistical correlation of TKa with clinical parameters and survival outcomes.
Main Results:
- Higher plasma TKa levels significantly associated with poorer baseline characteristics (ECOG status, M1c-d disease, elevated LDH).
- Lower response rate (30.3% vs 63.2%) and shorter PFS (12.6 vs 19.9 months) observed in high TKa group.
- Significantly worse overall survival (18.5 months vs >60 months) in patients with high pretreatment plasma TKa.
Conclusions:
- Elevated pretreatment plasma TKa is linked to adverse prognostic factors and poorer outcomes in ICI-treated melanoma.
- Plasma TKa emerges as a promising novel biomarker for melanoma.
- Further research is needed to establish TKa's definitive role as a prognostic and predictive marker.
