因为免疫检查点抑制剂(ICIs)对黑色素瘤患者的一部分有效,识别对ICIs有反应的黑色素瘤亚型至关重要.我们使用6个黑素瘤队列的转录组数据集,根据28个免疫细胞的富集水平进行聚类分析以鉴定黑素瘤的免疫亚型。包括四个未接受ICIs治疗的队列和两个接受ICIs治疗的队列。我们确定了三种免疫亚型(Im-H,Im-M,和Im-L),在这些队列中重现。Im-H表现出强烈的免疫特征,低干性和扩散潜力,基因组稳定性,高免疫治疗反应率,预后良好。Im-L表现出微弱的免疫特征,高干性和扩散潜力,基因组不稳定性,低免疫治疗反应率,预后不良。Im-H高度富集的途径包括免疫,MAPK,凋亡,钙,VEGF,细胞粘附分子,病灶粘连,间隙连接,和PPAR。Im-L中高度富集的途径包括河马,细胞周期,还有ErbB.拷贝数改变与黑色素瘤的免疫特征呈负相关,而肿瘤突变负荷无显著相关性。与有利的免疫治疗反应相关的分子特征包括免疫促进特征和PPAR的途径。MAPK,VEGF,钙,和糖酵解/糖异生。我们的数据重新获得了黑色素瘤的免疫异质性,并为黑色素瘤的免疫治疗提供了临床意义。
Because immune checkpoint inhibitors (ICIs) are effective for a subset of melanoma patients, identification of melanoma subtypes responsive to ICIs is crucial. We performed clustering analyses to identify immune subtypes of melanoma based on the enrichment levels of 28 immune cells using transcriptome datasets for six melanoma cohorts, including four cohorts not treated with ICIs and two cohorts treated with ICIs. We identified three immune subtypes (Im-H, Im-M, and Im-L), reproducible in these cohorts. Im-H displayed strong immune signatures, low stemness and proliferation potential, genomic stability, high immunotherapy response rate, and favorable prognosis. Im-L showed weak immune signatures, high stemness and proliferation potential, genomic instability, low immunotherapy response rate, and unfavorable prognosis. The pathways highly enriched in Im-H included immune, MAPK, apoptosis, calcium, VEGF, cell adhesion molecules, focal adhesion, gap junction, and PPAR. The pathways highly enriched in Im-L included Hippo, cell cycle, and ErbB. Copy number alterations correlated inversely with immune signatures in melanoma, while tumor mutation burden showed no significant correlation. The molecular features correlated with favorable immunotherapy response included immune-promoting signatures and pathways of PPAR, MAPK, VEGF, calcium, and glycolysis/gluconeogenesis. Our data recapture the immunological heterogeneity in melanoma and provide clinical implications for the immunotherapy of melanoma.