小柯机器人

美国国立卫生研究院Glenn Merlino、Chi-Ping Day和Maxwell P. Lee研究团队，合作开发了可用于预测黑色素瘤对免疫疗法临床反应的多模型临床前平台。这一研究成果在线发表在2020年4月13日出版的《自然—医学》上。

研究人员表征了一组同系小鼠模型，其具有人类黑素瘤的各种分子和表型亚型，并揭示了它们对免疫检查点封锁（ICB）的不同反应范围。

对基因组、转录组和肿瘤浸润免疫细胞谱的比较分析发现与临床观察的结果一致，并验证了T细胞功能障碍和排除过程与耐药的相关性。

值得注意的是，通过全基因组表达分析，研究人员发现黑色素细胞的可塑性可预测患者对ICB的预后反应，这表明黑色素瘤的多能性和分化状态可以决定ICB的疗效。

研究人员建立的比较临床前平台揭示了黑色素瘤的临床行为，其可用于确定改善患者治疗的机制和策略。

据介绍，尽管免疫疗法彻底改变了癌症的治疗方法，但只有一部分患者表现出持久的临床益处。尚不存在精准的预测生物标志物和克服耐药性的靶点，这突出了针对系统评估建立可靠免疫耐受模型的紧迫性。

附：英文原文

Title: Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy

Author: Eva Prez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Smith, Sung Chin, Khiem C. Lam, Andres Thorkelsson, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Shyam K. Sharan, Terry Van Dyke, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino

Issue&Volume: 2020-04-13

Abstract: Although immunotherapy has revolutionized cancer treatment, only a subset of patients demonstrate durable clinical benefit. Definitive predictive biomarkers and targets to overcome resistance remain unidentified, underscoring the urgency to develop reliable immunocompetent models for mechanistic assessment. Here we characterize a panel of syngeneic mouse models, representing a variety of molecular and phenotypic subtypes of human melanomas and exhibiting their diverse range of responses to immune checkpoint blockade (ICB). Comparative analysis of genomic, transcriptomic and tumor-infiltrating immune cell profiles demonstrated alignment with clinical observations and validated the correlation of T cell dysfunction and exclusion programs with resistance. Notably, genome-wide expression analysis uncovered a melanocytic plasticity signature predictive of patient outcome in response to ICB, suggesting that the multipotency and differentiation status of melanoma can determine ICB benefit. Our comparative preclinical platform recapitulates melanoma clinical behavior and can be employed to identify mechanisms and treatment strategies to improve patient care.

DOI: 10.1038/s41591-020-0818-3

Source: https://www.nature.com/articles/s41591-020-0818-3

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex