文章：

晚期黑色素瘤对PD-1抑制剂反应的多组学特征分析

Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma

原文发布日期：3 September 2023

DOI: 10.3390/cancers15174407

类型: Article

开放获取: 是

英文摘要：

Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment.

摘要翻译： 

免疫疗法改善了晚期黑色素瘤患者的生存率，其中40%成为长期应答者。然而，并非所有患者都对免疫疗法产生应答。我们仍需进一步了解免疫疗法应答及耐药的相关机制。本研究通过高通量蛋白质组学和RNA测序技术，对52例接受抗PD-1抑制剂治疗的晚期黑色素瘤患者的临床石蜡样本进行分析。基于概率图模型的多组学网络分析显示，内质网蛋白质加工与抗原呈递机制相关蛋白组成的节点活性在应答者中显著高于无应答者；获得完全或部分缓解患者的免疫及炎症反应节点活性也更为活跃。同时研究确定了基于两种蛋白（AMBP与PDSM5）的总生存期预测模型。综上所述，晚期黑色素瘤对抗PD-1疗法的应答与内质网蛋白质加工过程及免疫炎症反应相关基因密切相关，而双蛋白预测模型可有效评估晚期疾病患者的生存预后。对黑色素瘤免疫疗法应答及耐药机制的分子特征解析，将为不响应此类治疗的患者建立替代治疗方案开辟新路径。

原文链接：

Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma