Follicular lymphoma (FL) is a generally incurable malignancy that evolves from developmentally blocked germinal center (GC) B cells. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Dynamic interactions between tumor B cells and the tumor microenvironment (TME) are hypothesized to contribute to the broad spectrum of clinical behaviors observed among FL patients. Despite the urgent need, existing clinical tools do not reliably predict disease behavior. Using a multi-modal strategy, we examined cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes in FL patients enrolled onto a prospective clinical trial. By leveraging the strengths of each platform, we identify several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk FL patients. These features include stromal desmoplasia and changes to the follicular growth pattern present 20 months before first progression and first relapse.

中文翻译：

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滤泡性淋巴瘤的多组学分析揭示了高危患者组织结构的变化和基质重塑的增强

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 细胞经历显着的基因变化并广泛重塑淋巴微环境。据推测，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。尽管需求迫切，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，我们检查了参与前瞻性临床试验的 FL 患者的细胞内在和外在因素，这些因素控制着 FL 患者的进展和治疗结果。通过利用每个平台的优势，我们确定了一些肿瘤特异性特征和微环境模式，这些特征和微环境模式在经历早期复发的个体（最高风险的 FL 患者）中丰富。这些特征包括基质结缔组织增生和首次进展和首次复发前 20 个月出现的毛囊生长模式的变化。