Interleukin-18 Is a Prognostic Biomarker Correlated with CD8+ T Cell and Natural Killer Cell Infiltration in Skin Cutaneous Melanoma
Interleukin-18 Is a Prognostic Biomarker Correlated with CD8+ T Cell and Natural Killer Cell Infiltration in Skin Cutaneous Melanoma
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白介素18是皮肤黑色素瘤中CD8+T细胞和自然杀伤细胞浸润相关的预后生物标志物
DOI：
10.3390/jcm8111993
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发表时间：
2019-11-01
影响因子：
3.9
通讯作者：
Kim, Kyung Eun
中科院分区：
文献类型：
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作者：
Gil, Minchan;Kim, Kyung Eun
白细胞介素-18 （IL-18）是一种增强先天和适应性免疫反应的细胞因子。尽管关于IL-18在黑色素瘤进展中的作用有相互矛盾的报道，但IL-18表达的临床相关性尚未得到全面研究。在这项研究中，我们利用各种数据库中公开的癌症基因表达数据，研究了IL-18表达及其与黑色素瘤患者生存和免疫细胞浸润的相关性。il - 18 mRNA在黑色素瘤组织中的表达明显低于正常组织。Kaplan-Meier生存分析显示，il - 18表达与患者生存呈正相关。为了研究il - 18表达增加患者生存率的可能机制，我们随后评估了il - 18表达与免疫细胞浸润水平之间的相关性。il - 18的表达显著增加了各种免疫细胞的浸润，特别是CD8(+) T细胞和自然杀伤细胞（NK）细胞，它们是细胞溶解效应细胞。此外，穿孔素和颗粒酶B两种细胞溶解分子的表达水平与il - 18的表达呈显著正相关。总之，本研究首次提供了IL-18表达对黑色素瘤患者生存具有预后价值的证据，并且与CD8(+) T和NK细胞浸润密切相关，提示IL-18可作为预测黑色素瘤预后的生物标志物。
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. IL18 mRNA expression was found to be significantly lower in melanoma tissues than normal tissues. Kaplan-Meier survival analysis showed that IL18 expression was positively correlated with patient survival. To investigate the possible mechanisms by which IL18 expression increased patient survival, we then assessed the correlation between IL18 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 IL18 expression. Additionally, the expression levels of two cytolytic molecules including perforin and granzyme B were significantly positively correlated with IL18 expression. Collectively, this study provides the first evidence that IL18 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.