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要想实现免疫治疗的个性化,任重道远。

It's a long way to the top (if you want to personalize immunotherapy).

机构信息

Department of Medicine III, Laboratory for Experimental Leukemia and Lymphoma Research (ELLF), Ludwig-Maximilians-University, Max-Lebsche Platz 30, 81377 Munich, Germany.

Department of Medicine III, Laboratory for Experimental Leukemia and Lymphoma Research (ELLF), Ludwig-Maximilians-University, Max-Lebsche Platz 30, 81377 Munich, Germany ; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

J Immunother Cancer. 2017 Jan 17;5:6. doi: 10.1186/s40425-016-0207-0. eCollection 2017.

Abstract

Harnessing the immune system to attack tumor cells by targeting tumor-associated or -preferably- tumor-specific antigens has emerged as a promising but challenging treatment option for malignant lymphomas. Follicular lymphoma is among the most common lymphomas worldwide and remains incurable for most patients. Considered to be an immunogenic disease it represents an interesting disease entity for various immunotherapeutic approaches. In an article published in the May issue of , Nielsen and colleagues provided important proof-of-principle data on the immunogenicity of follicular lymphoma that might represent a first step towards personalized adoptive immunotherapies in this disease. The authors combined targeted next-generation sequencing and in silico analyses to explore the concept of somatic neoepitope prediction. Neoantigen-specific CD8 T-cells could be identified in a small subset of patients selected for in vitro immunogenicity experiments, however at remarkably low frequencies and in only a few patients at single time-points. Of note, the immunogenic neoepitopes were derived from mutant and , two genes that have previously been shown to be functionally and prognostically relevant in this disease. In this commentary we discuss the promises but also the challenges of how to translate these findings into clinical practice.

摘要

通过靶向肿瘤相关或-最好是-肿瘤特异性抗原来利用免疫系统攻击肿瘤细胞,已成为治疗恶性淋巴瘤的一种有前途但具有挑战性的治疗选择。滤泡性淋巴瘤是全球最常见的淋巴瘤之一,大多数患者仍然无法治愈。滤泡性淋巴瘤被认为是一种免疫原性疾病,它代表了各种免疫治疗方法的一个有趣的疾病实体。在发表于五月刊的一篇文章中,Nielsen 及其同事提供了关于滤泡性淋巴瘤免疫原性的重要原理验证数据,这可能代表着朝着该疾病的个体化过继性免疫治疗迈出了第一步。作者结合靶向下一代测序和计算机分析来探索体细胞新抗原预测的概念。在选择进行体外免疫原性实验的一小部分患者中,可以识别出新抗原特异性 CD8 T 细胞,但频率非常低,而且仅在少数患者的单个时间点上。值得注意的是,这些免疫原性新抗原来自突变的 和 ,这两个基因以前在该疾病中显示出功能和预后相关性。在这篇评论中,我们讨论了如何将这些发现转化为临床实践的前景和挑战。

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