Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro", University of Palermo, Palermo, Italy.
Histopathology Unit, Institute of Molecular Oncology Foundation (IFOM) ETS - The AIRC Institute of Molecular Oncology, Milan, Italy.
Front Immunol. 2023 Aug 23;14:1207959. doi: 10.3389/fimmu.2023.1207959. eCollection 2023.
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.
我们已经为反应性淋巴组织的不同微区的转录特征建立了一个伪时间排序，即生发中心暗区（DZ）、生发中心亮区（LZ）和滤泡周围区（Peri）。通过利用源自 DZ、LZ 和 Peri 的功能微环境的伪时间轨迹，我们对弥漫性大 B 细胞淋巴瘤病例的转录组进行了排序。所得伪时间轨迹的顶点，其特征是富含 TNFR 信号和抑制性免疫检查点过表达的分子程序，截获了一个离散的滤泡周围生物学。这一观察结果与富含未分类/3 型 COO 类别的 DLBCL 病例有关，这引发了关于这类特殊病例潜在的额外 GC 微环境印记的问题。本报告就功能淋巴组织微环境的转录谱与弥漫性大 B 细胞淋巴瘤中起源细胞的不断发展的概念之间的关系提供了一个发人深省的视角。
