Interleukin-18 Is a Prognostic Biomarker Correlated with CD8+ T Cell and Natural Killer Cell Infiltration in Skin Cutaneous Melanoma

Abstract

Interleukin-18 (IL-18) is a cytokine that enhances innate and adaptive immune responses. Although there are conflicting reports about the roles of IL-18 in melanoma progression, the clinical relevance of IL-18 expression has not been comprehensively studied. In this study, we investigated IL-18 expression and its correlation with patient survival and immune cell infiltration in melanoma using cancer gene expression data publicly available through various databases. <i>IL18</i> mRNA expression was found to be significantly lower in melanoma tissues than normal tissues. Kaplan-Meier survival analysis showed that <i>IL18</i> expression was positively correlated with patient survival. To investigate the possible mechanisms by which <i>IL18</i> expression increased patient survival, we then assessed the correlation between <i>IL18</i> expression and immune cell infiltration levels. Infiltration of various immune cells, especially CD8⁺ T and natural killer (NK) cells, which are cytolytic effector cells, was significantly increased by <i>IL18</i> expression. Additionally, the expression levels of two cytolytic molecules including perforin and granzyme B were significantly positively correlated with <i>IL18</i> expression. Collectively, this study provides the first evidence that <i>IL18</i> expression has prognostic value for melanoma patient survival and is strongly correlated with CD8⁺ T and NK cell infiltration, suggesting the role of IL-18 as a biomarker for predicting melanoma prognosis.