代谢组学适应和与免疫检查点阻断治疗生存相关的因素。
Metabolomic adaptations and correlates of survival to immune checkpoint blockade.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
出版信息
Nat Commun. 2019 Sep 25;10(1):4346. doi: 10.1038/s41467-019-12361-9.
Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase (IDO/TDO) inhibitors.
尽管免疫检查点抑制剂取得了显著的成功，但大多数癌症患者仍未从中获得持久的益处。在这里，为了研究免疫检查点阻断反应中的代谢变化，我们全面分析了接受 nivolumab（一种针对程序性细胞死亡蛋白 1（PD1）的抗体）治疗的晚期黑色素瘤和肾细胞癌患者的血清代谢物。我们发现血清犬尿氨酸/色氨酸比值升高是一种与总生存时间更差相关的适应性耐药机制。这提倡在免疫治疗临床试验中进行患者分层和代谢监测，包括将 PD1 阻断与吲哚胺 2,3-双加氧酶/色氨酸 2,3-双加氧酶（IDO/TDO）抑制剂联合使用的临床试验。
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