我们已经建立了反应性淋巴组织中不同微区的转录标记的伪时序排序，即生发中心暗区（DZ）、生发中心明亮区（LZ）和滤泡周围区（Peri）。通过利用从DZ、LZ和Peri的功能微环境中得出的伪时间轨迹，我们已经对弥漫性大B细胞淋巴瘤病例的转录组进行了排序。结果伪时间轨迹的高点，特征是TNFR信号通路和抑制性免疫检查点过度表达的分子程序富集，与离散的滤泡周围生物学相交。这种观察与富含不可分类/3型COO类别的DLBCL病例相关，引发了关于这个特殊病例群体可能具有额外的生发中心微环境印记的问题。本报告为弥漫性大B细胞淋巴瘤中功能淋巴组织微环境转录谱与起源细胞概念的不断发展之间的关系提供了引人思考的视角。版权所有 © 2023 Tripodo, Bertolazzi, Cancila, Morello和Iannitto。

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.Copyright © 2023 Tripodo, Bertolazzi, Cancila, Morello and Iannitto.