小柯机器人

美国加州大学欧文分校Lisa E. Wagar小组开发出用于评估和靶向滤泡淋巴瘤肿瘤免疫微环境的人类淋巴瘤类器官模型。相关论文于2024年2月22日在线发表在《细胞—干细胞》杂志上。

研究人员表示，滤泡性淋巴瘤（FL）肿瘤微环境（TME）的异质性会影响临床疗效。目前的免疫治疗策略，包括基于抗体和细胞的疗法，可不同程度地克服促肿瘤生成机制，以达到持续控制疾病的目的。模拟完整的FL TME及其原生的、合成的肿瘤浸润白细胞是一项重大挑战。

研究人员描述了一种培养患者衍生淋巴瘤器官组织（PDLO）的器官组织培养方法，其中包括来自原生FL TME的细胞。研究人员通过成功培养来自不同患者的冷冻FL标本，确定了这种方法的稳健性，并证明了TME细胞组成、肿瘤体细胞突变、基因表达谱和B/T细胞受体动态在3周内的稳定性。用CD3:CD19和CD3:CD20治疗性双特异性抗体处理的PDLO显示了B细胞杀伤和T细胞活化。这一稳定的系统提供了一个强大的平台，可通过患者特异性建模、高通量筛选、TME特征识别和治疗反应评估来推进FL的精准医疗工作。

附：英文原文

Title: A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment

Author: Jenna M. Kastenschmidt, Joseph G. Schroers-Martin, Brian J. Sworder, Suhas Sureshchandra, Michael S. Khodadoust, Chih Long Liu, Mari Olsen, David M. Kurtz, Maximilian Diehn, Lisa E. Wagar, Ash A. Alizadeh

Issue&Volume: 2024-02-22

Abstract: Heterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We define the robustness of this method by successfully culturing cryopreserved FL specimens from diverse patients and demonstrate the stability of TME cellular composition, tumor somatic mutations, gene expression profiles, and B/T cell receptor dynamics over 3 weeks. PDLOs treated with CD3:CD19 and CD3:CD20 therapeutic bispecific antibodies showed B cell killing and T cell activation. This stable system offers a robust platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.

DOI: 10.1016/j.stem.2024.01.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00042-0

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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