Li Xubin, Singhal Kartik, Deng Qing, Chihara Dai, Russler-Germain David, Harkins R Andrew, Henderson Jared, Arita Kotaro, Kizhakeyil Atish, Sun Ryan, Lakra Priya, Hussein Usama, Foltz Jennifer A, Wilson Ashley, Schmidt Evelyn, Nizamuddin Imran, Dinh Tommy, Kesaraju Akhil, Hamilton Mark P, Allen Carl, Gandhi Maher K, Tobin Joshua, Jiang Aixiang, Hilton Laura, Scott David W, Vega Francisco, Flowers Christopher R, Westin Jason R, Griffith Obi L, Fehniger Todd A, Griffith Malachi, Green Michael R
Department of Lymphoma and Myeloma, University of Texas (UT) MD Anderson Cancer Center, Houston, TX, USA; Lymphoid Malignancies Program, UT MD Anderson Cancer Center, Houston, TX, USA.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Cancer Cell. 2025 Jul 14;43(7):1347-1364.e13. doi: 10.1016/j.ccell.2025.06.002. Epub 2025 Jun 18.
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.
大B细胞淋巴瘤（LBCL）是临床和生物学上异质性的淋巴恶性肿瘤，其复杂的微环境是疾病病因的核心。在此，我们对232份肿瘤和对照活检样本进行了单核多组学分析，以表征LBCL肿瘤中存在的各种细胞类型和亚群，有效捕获了淋巴、髓系和非造血细胞区室。细胞亚群在由以下定义的典型淋巴瘤微环境原型图谱（LymphoMAPs）中共同出现：（1）T细胞稀少，癌症相关成纤维细胞和肿瘤相关巨噬细胞（FMAC）频率高；（2）具有幼稚和记忆T细胞的淋巴结结构细胞类型（LN）；或（3）活化的巨噬细胞和耗竭的CD8 T细胞（TEX）。不同的细胞间通讯模式支撑了定义原型的细胞亚群的转录表型，分别导致T细胞的排除、支持或抑制。与此一致的是，LymphoMAPs与CD19嵌合抗原受体（CAR）T细胞治疗后的显著不同临床结果相关。
