Spatial transcriptomics unveils immune cellular ecosystems associated with patient survival in diffuse large B-cell lymphoma

bioRxiv - Immunology Pub Date : 2024-09-16 DOI:10.1101/2024.09.16.613252

Alba Díaz Herrero, Hector Fernando Pelaez-Prestel, Lucile Massenet-Regad, Maëva Veyssiere, Julien Calvani, Caterina Cristinelli, Jacqueline Lehmann-Che, Véronique Meignin, Catherine Thieblemont, Véronique Blanc, Vassili Soumelis, Pierre Tonnerre

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Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma for which current therapeutic strategies remain insufficient. The diffuse nature of DLBCL, lacking distinct tissue structures, represents a challenge to elucidate the cellular organization and interactions within the tumor microenvironment (TME). In this study, we applied spatial transcriptomics to identify spatially-resolved gene expression profiles in 10 DLBCL tissue samples, identifying distinct immune cell infiltration and colocalization patterns. These profiles were classified into six cellular ecosystems (Cell-Eco) that differ in cellular composition, functional patterns, and neighborhood characteristics. The spatially-resolved Cell-Eco signatures provided prognostic scores that stratified patients with different overall survival rates. We also found that C1q+ tumor-associated macrophages are the primary cells interacting with malignant B cells and influencing the spatial architecture of the TME. This study provides novel biological insights into the complexity of the TME in DLBCL and highlights the potential prognostic value of its spatial organization.

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空间转录组学揭示了与弥漫大B细胞淋巴瘤患者生存相关的免疫细胞生态系统

弥漫性大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤中最常见的亚型，目前的治疗策略仍不足以治愈这种淋巴瘤。DLBCL 具有弥漫性，缺乏明显的组织结构，这给阐明肿瘤微环境（TME）内的细胞组织和相互作用带来了挑战。在这项研究中，我们应用空间转录组学鉴定了 10 个 DLBCL 组织样本中空间分辨的基因表达谱，确定了不同的免疫细胞浸润和共聚焦模式。这些图谱被分为六个细胞生态系统（Cell-Eco），它们在细胞组成、功能模式和邻域特征方面各不相同。空间分辨的细胞生态特征提供了预后评分，可对不同总生存率的患者进行分层。我们还发现，C1q+肿瘤相关巨噬细胞是与恶性B细胞相互作用并影响TME空间结构的主要细胞。这项研究为了解 DLBCL 中 TME 的复杂性提供了新的生物学见解，并强调了其空间组织的潜在预后价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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bioRxiv - Immunology

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