terraFlow 是一种高参数分析工具,揭示了经典霍奇金淋巴瘤中 T 细胞耗竭和细胞因子产生功能失调的情况。
terraFlow, a high-parameter analysis tool, reveals T cell exhaustion and dysfunctional cytokine production in classical Hodgkin's lymphoma.
发表日期:2024 Aug 10
作者:
Daniel Freeman, Catherine Diefenbach, Linda Lam, Tri Le, Jason Alexandre, Bruce Raphael, Michael Grossbard, David Kaminetzky, Jia Ruan, Pratip K Chattopadhyay
来源:
Cell Reports
摘要:
免疫细胞表达种类繁多的蛋白质;通过测量这些的组合,可以精确地识别影响疾病的细胞类型。我们开发了 terraFlow,这是一个通过组合蛋白表达详尽定义细胞亚群的平台。我们使用以检查点为中心和以功能为中心的高参数面板,研究了经典霍奇金淋巴瘤 (cHL),其中全身性 T 细胞尚未得到详细研究。 terraFlow 揭示了患者的免疫扰动,包括治疗前活化、耗尽和白细胞介素 (IL)-17 表型升高,以及早期、干扰素 (IFN)γ 和肿瘤坏死因子 (TNF) T 细胞减少;治疗后仍然存在许多扰动。 terraFlow 比其他工具发现了更多与疾病相关的差异,通常具有更好的预测能力,并且包括非门控方法,消除了耗时和主观的手动阈值。它还报告了一种识别区分研究组的最小标记集的方法。我们的结果为过去关于 cHL 免疫缺陷的报道提供了机制支持,并证明了 terraFlow 在免疫治疗和生物标志物研究中的价值。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
Immune cells express an incredible variety of proteins; by measuring combinations of these, cell types influencing disease can be precisely identified. We developed terraFlow, a platform that defines cell subsets exhaustively by combinatorial protein expression. Using high-parameter checkpoint-focused and function-focused panels, we studied classical Hodgkin's lymphoma (cHL), where systemic T cells have not been investigated in detail. terraFlow revealed immune perturbations in patients, including elevated activated, exhausted, and interleukin (IL)-17+ phenotypes, along with diminished early, interferon (IFN)γ+, and tumor necrosis factor (TNF)+ T cells before treatment; many perturbations remained after treatment. terraFlow identified more disease-associated differences than other tools, often with better predictive power, and included a non-gating approach, eliminating time-consuming and subjective manual thresholds. It also reports a method to identify the smallest set of markers distinguishing study groups. Our results provide mechanistic support for past reports of immune deficiency in cHL and demonstrate the value of terraFlow in immunotherapy and biomarker studies.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.