德克萨斯大学Michael R. Green课题组报道了大B细胞淋巴瘤微环境原型图。相关论文于2025年6月18日发表在《癌细胞》杂志上。

该研究组对232例肿瘤和对照活检进行了单核多组分析，以表征LBCL肿瘤中存在的不同细胞类型和亚群，有效地捕获淋巴细胞、髓细胞和非造血细胞区室。细胞亚群共同发生在典型淋巴瘤微环境原型谱（淋巴瘤MAPs）中，定义如下；(1) T细胞的稀疏性和癌症相关成纤维细胞和肿瘤相关巨噬细胞（FMAC）的高频率；(2)淋巴结结构细胞类型为幼稚T细胞和记忆T细胞（LN）；或(3)激活巨噬细胞和耗尽CD8⁺ T细胞（TEX）。不同的细胞-细胞通讯模式支撑了原型定义细胞亚群的转录表型，分别导致T细胞的排斥、支持或抑制。与此一致的是，在CD19嵌合抗原受体（CAR） T细胞治疗后，淋巴瘤MAPs与显著不同的临床结果相关。

据了解，大B细胞淋巴瘤（LBCL）是临床上和生物学上异质性的淋巴样恶性肿瘤，具有复杂的微环境，是疾病病因学的核心。

附：英文原文

Title: Large B cell lymphoma microenvironment archetype profiles

Author: Xubin Li, Kartik Singhal, Qing Deng, Dai Chihara, David Russler-Germain, R. Andrew Harkins, Jared Henderson, Kotaro Arita, Atish Kizhakeyil, Ryan Sun, Priya Lakra, Usama Hussein, Jennifer A. Foltz, Ashley Wilson, Evelyn Schmidt, Imran Nizamuddin, Tommy Dinh, Akhil Kesaraju, Mark P. Hamilton, Carl Allen, Maher K. Gandhi, Joshua Tobin, Aixiang Jiang, Laura Hilton, David W. Scott, Francisco Vega, Christopher R. Flowers, Jason R. Westin, Obi L. Griffith, Todd A. Fehniger, Malachi Griffith, Michael R. Green

Issue&Volume: 2025-06-18

Abstract: Large B cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies with complex microenvironments that are central to disease etiology. Here, we have employed single-nucleus multiome profiling of 232 tumor and control biopsies to characterize diverse cell types and subsets that are present in LBCL tumors, effectively capturing the lymphoid, myeloid, and non-hematopoietic cell compartments. Cell subsets co-occurred in stereotypical lymphoma microenvironment archetype profiles (LymphoMAPs) defined by; (1) a sparsity of T cells and high frequencies of cancer-associated fibroblasts and tumor-associated macrophages (FMAC); (2) lymph node architectural cell types with naive and memory T cells (LN); or (3) activated macrophages and exhausted CD8+ T cells (TEX). Divergent patterns of cell-cell communication underpinned the transcriptional phenotypes of archetype-defining cell subsets resulting in exclusion, support, or suppression of T cells, respectively. Consistent with this, LymphoMAPs were associated with significantly different clinical outcomes following CD19 chimeric antigen receptor (CAR) T cell therapy.

DOI: 10.1016/j.ccell.2025.06.002

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00228-4