Immune checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, up to 60% of treated patients do not respond to ICI and/or develop immune-related adverse events (irAEs). Currently, robust and reliable biomarker to predict response and/or occurrence of irAEs to ICI are missing. Herein, we wanted to explore whether germline variants (SNPs) could predict the clinical outcomes of melanoma patients treated with ICIs. We performed a whole exome sequencing using gDNA isolated from blood, from a discovery cohort of 57 patients with metastatic melanoma. The top associations were then tested in a validation cohort of 57 patients. Our work suggests that individual germline genetic variants have no or weak impact on the response to ICIs. Only, variants in IL1RL1 have a significant impact in treatment response. The role of IL1RL1 in the immune response against melanoma and as a theranostic marker warrants further investigations.

中文翻译：

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外显子区域的种系变异对晚期黑色素瘤的免疫检查点阻断临床结果的影响有限

免疫检查点抑制 (ICI) 治疗可改善转移性黑色素瘤的预后；然而，多达 60% 的接受治疗的患者对 ICI 没有反应和/或发生免疫相关不良事件 (irAE)。目前，缺乏可靠且可靠的生物标志物来预测 ICI 的反应和/或 irAE 的发生。在这里，我们想探索生殖系变异 (SNP) 是否可以预测接受 ICI 治疗的黑色素瘤患者的临床结果。我们使用从 57 名转移性黑色素瘤患者的发现队列中分离出的血液 gDNA 进行了全外显子组测序。然后在 57 名患者的验证队列中测试了顶级关联。我们的工作表明，个体种系遗传变异对 ICI 的反应没有影响或影响很小。只有 IL1RL1 中的变体对治疗反应有显着影响。