美国贝塞斯达国立卫生研究院免疫系统生物学实验室Andrea J. Radtke团队近期取得重要工作进展，他们通过滤泡性淋巴瘤的多组学分析，揭示了高风险患者组织结构的改变和间质重塑的增强。相关研究成果于2024年2月29日在线发表于《癌细胞》杂志上。

据介绍，滤泡性淋巴瘤（FL）是一种通常无法治愈的恶性肿瘤，由发育受阻的生发中心（GC）B细胞演变而来。为了促进生存和免疫逃逸，肿瘤B细胞经历显著的遗传变化并广泛重塑淋巴微环境。假设肿瘤B细胞和肿瘤微环境（TME）之间的动态相互作用有助于在FL患者中观察到的广泛临床行为。尽管迫切需要，但现有的临床工具并不能可靠地预测疾病行为。

使用多模式策略，研究人员探讨了参与前瞻性临床试验的FL患者中控制进展和治疗结果的细胞内在和外在因素。通过利用每个平台的优势，研究人员确定了一些肿瘤特异性特征和微环境模式，这些特征和模式在经历早期复发的个体中富集，这些个体是最高危的FL患者。这些特征包括在第一次进展和第一次复发前20个月出现的，间质结缔组织增生和滤泡生长模式的改变。

附：英文原文

Title: Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients

Author: Andrea J. Radtke, Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergey Isaev, Daniil Wiebe, Anna Sharun, Alexander Sarachakov, Grigory Perelman, Yaroslav Lozinsky, Ziv Yaniv, Bradley C. Lowekamp, Emily Speranza, Li Yao, Stefania Pittaluga, Arthur L. Shaffer, Danny Jonigk, James D. Phelan, Theresa Davies-Hill, Da Wei Huang, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Ataullakhanov, Nathan Fowler, Michael Kelly, Jagan Muppidi, Jeremy L. Davis, Jonathan M. Hernandez, Wyndham H. Wilson, Elaine S. Jaffe, Louis M. Staudt, Mark Roschewski, Ronald N. Germain

Issue&Volume: 2024-02-29

Abstract: Follicular lymphoma (FL) is a generally incurable malignancy that evolves from developmentallyblocked germinal center (GC) B cells. To promote survival and immune escape, tumorB cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment.Dynamic interactions between tumor B cells and the tumor microenvironment (TME) arehypothesized to contribute to the broad spectrum of clinical behaviors observed amongFL patients. Despite the urgent need, existing clinical tools do not reliably predictdisease behavior. Using a multi-modal strategy, we examined cell-intrinsic and -extrinsicfactors governing progression and therapeutic outcomes in FL patients enrolled ontoa prospective clinical trial. By leveraging the strengths of each platform, we identifyseveral tumor-specific features and microenvironmental patterns enriched in individualswho experience early relapse, the most high-risk FL patients. These features includestromal desmoplasia and changes to the follicular growth pattern present 20 monthsbefore first progression and first relapse.

DOI: 10.1016/j.ccell.2024.02.001

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00045-X