Cytokine Profiling in Cutaneous Melanoma: The Emerging Role of Interleukins in Prognostic Stratification with an...

Background: Cutaneous melanoma is an aggressive malignancy driven by complex interactions between tumor cells and the host immune system. Tumor progression is shaped not only by intrinsic tumor characteristics but also by immune-mediated processes within the tumor microenvironment. Cytokines, particularly interleukins, are key regulators of inflammation, immune cell recruitment, and tumor behavior. Cytokine profiling provides an integrated assessment of soluble immune mediators from tumor and stromal cells, reflecting both local and systemic immune responses. Methods: This narrative review summarizes and synthesizes the current literature addressing the biological and clinical relevance of selected interleukins, including IL-6, IL-8, IL-10, IL-2, IL-17, and IL-18, in cutaneous melanoma. Published data were evaluated with a focus on their immunomodulatory functions and potential implications for prognostic assessment. Results: Interleukins demonstrated distinct and context-dependent prognostic and predictive relevance in cutaneous melanoma. Elevated IL-2 levels correlated with sentinel lymph node positivity, supporting its prognostic value in early disease. Increased circulating IL-6 and IL-8 were consistently associated with tumor burden, advanced disease, and reduced survival. IL-10 expression reflected tumor progression and immune modulation. IL-17 signatures predicted response to combined immune checkpoint inhibition, particularly in BRAFV600-mutant melanoma. IL-18 exhibited dual roles, associating with both immune activation and favorable outcomes depending on tumor context. Conclusions: Interleukin profiling offers a biologically relevant framework for understanding immune regulation in cutaneous melanoma. Integrating interleukin signatures into prognostic models may support more refined risk stratification and advance the implementation of personalized medicine approaches in melanoma management.