# Evaluation of Cytokine Profile in Canine Malignant Oral Melanoma

## TL;DR

This study examines cytokine levels in dogs with oral melanoma to understand their role in disease progression and treatment outcomes.

## Contribution

The study identifies specific cytokine patterns associated with melanoma types and metastasis in dogs, offering insights for human cancer research.

## Key findings

- Post-surgery, GM-CSF, IFN-γ, MCP-1, IL-18, and IL-2 levels increased significantly in dogs with oral melanoma.
- IL-7 and MCP-1 levels were higher in remission samples compared to melanoma samples.
- Amelanotic melanoma samples showed higher IL-6, IL-10, and IL-15 levels than melanotic samples.

## Abstract

Canine models have been recognized as valuable tools for studying various human cancers, including melanoma. Research on carcinogenesis and the development of innovative cancer therapies is progressing rapidly, leading to improved treatment options in veterinary medicine. Despite this progress, the prognostic role of cytokines in canine oncology remains insufficiently investigated. This prospective study reports on 10 cases of oral malignant melanoma (OMM) in dogs that underwent surgical treatment. Among them, four were diagnosed with melanotic and six with amelanotic melanoma. Serum samples were collected at baseline (prior to surgery), on the day of surgery, and subsequently every 3–4 months, accompanied by clinical examinations and thoracic radiographs. Concentrations of GM-CSF, IFN-γ, IL-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IP-10, KC-like, MCP-1, and TNFα were quantified. Follow-up samples indicated that after the removal of malignant melanoma, the serum levels of GM-CSF, IFN-γ, MCP-1, IL-18, and IL-2 increased significantly. In contrast, when comparing samples from dogs with oral malignant melanoma to those without the disease, concentrations of IL-7 and MCP-1 were significantly higher in the absence of disease samples than in the OMM samples. Furthermore, when comparing serum concentrations between samples from OMM patients with metastasis and those patients in remission, elevated levels of MCP-1 were associated with poorer overall survival due to the development of OMM metastasis. Lastly, a comparison of cytokines in samples from melanotic OMM and amelanotic OMM revealed that amelanotic OMM samples exhibited higher concentrations of IL-6, IL-10, and IL-15 compared to their melanotic counterparts. This study contributes to the evidence that canine models can offer valuable insights that may also translate into more effective and targeted treatments for human melanoma.

Ten dogs with oral malignant melanoma were evaluated and treated with surgery, of which four dogs were diagnosed with melanotic melanoma and six were diagnosed with amelanotic melanoma. Serum samples from oral malignant melanoma (OMM) were collected at baseline, the day of the surgery, and every 3–4 months, during which time a clinical examination and chest X-rays were performed. Concentrations of GM-CSF, IFN-γ, IL-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IP-10, KC-like, MCP-1, and TNFα were quantified. Follow-up samples indicated that after the removal of malignant melanoma, the serum levels of GM-CSF, IFN-γ, MCP-1, IL-18, and IL-2 increased significantly. In contrast, when comparing samples from dogs with OMM to those of patients in remission, the concentrations of IL-7 and MCP-1 were significantly higher in the remission samples than in the OMM samples. Furthermore, when comparing the serum concentrations between the OMM-metastasis samples and those patients in remission, elevated levels of MCP-1 were associated with poorer overall survival due to the development of OMM metastasis. Finally, a comparison of cytokines in the melanotic OMM and amelanotic OMM samples revealed that the amelanotic OMM samples exhibited higher concentrations of IL-6, IL-10, and IL-15 compared to the melanotic OMM samples.