肿瘤CD3⁺ B细胞通过单细胞和空间转录组学重塑DLBCL肿瘤微环境

摘要(中文译文)

本研究通过整合单细胞、单细胞核和空间转录组学数据，构建了弥漫性大B细胞淋巴瘤（DLBCL）的高分辨率多组学图谱。我们鉴定出一个此前未被认识、反复出现的恶性B细胞亚群，该亚群意外表达CD3——一种通常仅存在于T细胞上的蛋白。这一异常的CD3⁺ B细胞群体似乎由涉及五个关键调控基因（BCLAF1、CHURC1、FLI1、NFATC2和ELF2）的特定遗传回路驱动。空间和功能分析显示，这些细胞与巨噬细胞富集及M2极化相关，可能涉及TGF-信号通路，并促进免疫抑制性肿瘤微环境的形成。在临床上，CD3⁺ B细胞的丰度与疾病晚期、治疗反应差和生存期缩短相关。我们的研究结果支持存在一个具有T细胞样特征的CD3⁺ B细胞亚群，该亚群与肿瘤微环境重塑和不良临床结局相关，并提示FLI1和TGF-轴等分子决定因素可作为潜在的治疗靶点。

Abstract

This study constructs a high-resolution multi-omics map of Diffuse Large B-Cell Lymphoma (DLBCL) by integrating single-cell, single-nucleus, and spatial transcriptomics. We identified a previously unrecognized, recurrent subset of malignant B cells that unexpectedly express CD3, a protein typically found only on T cells. This unusual CD3⁺ B cell population appears to be driven by a specific genetic circuit involving five key regulatory genes: BCLAF1, CHURC1, FLI1, NFATC2, and ELF2. Spatial and functional analyses revealed that these cells are associated with macrophage enrichment and M2 polarization, potentially involving TGF- signaling and contributing to an immunosuppressive tumor microenvironment. Clinically, the abundance of CD3⁺ B cells was associated with advanced disease stage, poor treatment response, and reduced survival. Our findings support the presence of a CD3⁺ B cell subset with T cell-like features that is associated with tumor microenvironment remodeling and adverse clinical outcomes, highlighting molecular determinants like FLI1 and the TGF- axis as potential therapeutic targets.

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