Large B cell lymphoma microenvironment archetype profiles

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-06-18 DOI:10.1016/j.ccell.2025.06.002

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, Michael R. Green

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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.

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大B细胞淋巴瘤微环境原型图

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。在这里，我们对232例肿瘤和对照活组织检查采用单核多组分析来表征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ap）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）；(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ap与显著不同的临床结果相关。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.