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美国丹娜-法伯癌症研究所Catherine J. Wu研究组发现ZNF683标志着CD8+ T细胞群与Richter综合征(RS)抗PD-1治疗后的抗肿瘤免疫相关。这一研究成果于2023年9月21日发表在国际顶尖学术期刊《癌细胞》上。

为了发现应答的决定因素，他们分析了从6例RS患者纵向收集的17份骨髓样本中产生的单细胞转录组数据。应答与中间耗尽的CD8效应/效应记忆T细胞有关，该细胞以转录因子ZNF683的高表达为标志，被确定为从干细胞样记忆细胞进化而来，并从终末耗尽的细胞分化而来。

这一特征与来自抗PD-1反应性实体瘤的肿瘤浸润群体重叠。ZNF683直接靶向T细胞关键基因(TCF7、LMO2、CD69)，影响T细胞的细胞毒性和活化途径。对10例接受抗PD-1治疗的独立RS患者以及接受抗PD-1治疗的实体瘤患者的治疗前外周血进行分析，支持ZNF683high T细胞与反应的关联。

据介绍，与许多其他血液系统恶性肿瘤不同，RS是一种起源于惰性慢性淋巴细胞白血病的侵袭性B细胞淋巴瘤，对PD-1阻断有反应。

附：英文原文

Title: ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome

Author: Erin M. Parry, Camilla K. Lemvigh, Stephanie Deng, Nathan Dangle, Neil Ruthen, Binyamin A. Knisbacher, Julien Broséus, Sébastien Hergalant, Romain Guièze, Shuqiang Li, Wandi Zhang, Connor Johnson, Jaclyn Long, Shanye Yin, Lillian Werner, Annabelle Anandappa, Noelia Purroy, Satyen Gohil, Giacomo Oliveira, Pavan Bachireddy, Sachet A. Shukla, Teddy Huang, Joseph D. Khoury, Beenu Thakral, Michael Dickinson, Constantine Tam, Kenneth J. Livak, Gad Getz, Donna Neuberg, Pierre Feugier, Peter Kharchenko, William Wierda, Lars Rnn Olsen, Nitin Jain, Catherine J. Wu

Issue&Volume: 2023-09-21

Abstract: Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive Bcell lymphoma originating from indolent chronic lymphocytic leukemia, is responsiveto PD-1 blockade. To discover the determinants of response, we analyze single-celltranscriptome data generated from 17 bone marrow samples longitudinally collectedfrom 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effectormemory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminallyexhausted cells. This signature overlaps with that of tumor-infiltrating populationsfrom anti-PD-1 responsive solid tumors. ZNF683 is found to directly target key T cellgenes (TCF7, LMO2, CD69) and impact pathways of T cell cytotoxicity and activation. Analysis of pre-treatmentperipheral blood from 10 independent patients with RS treated with anti-PD-1, as wellas patients with solid tumors treated with anti-PD-1, supports an association of ZNF683high T cells with response.

DOI: 10.1016/j.ccell.2023.08.013

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00306-9

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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