The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma

IF 7.6 Q1 ONCOLOGY

Journal of the National Cancer Center Pub Date : 2025-04-01 DOI:10.1016/j.jncc.2025.02.001

Xiaomei Zhang , Zailin Yang , Xiaoqing Xie , Jun Li , Qing Xiao , Guofa Xu , Ben Ma , Xudong Xie , Yi Liu , Liuyue Zhai , Yifeng Tang , Huihui Fu , Sanxiu He , Tingting Liu , Dehong Huang , Censi Zeng , Yixing Zhou , Renzhi Hu , Binling Guo , Chaoyu Wang , Yao Liu

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Abstract

Background

Human immunodeficiency virus (HIV)-associated lymphomas (HAL), mainly aggressive B-cell lymphomas, pose a significant challenge in cancer research due to their multifaceted pathogenesis and aggressive clinical course. Despite the clinical importance, the genomic and immune characteristics of these lymphomas remain poorly elucidated.

Methods

We employed single-cell RNA sequencing (scRNA-seq) on lymph node samples from aggressive B-cell lymphomas, mainly including 6 cases of diffuse large B-cell lymphoma (DLBCL) and 5 cases of Burkitt lymphoma (BL) from people living with HIV (PLWH), along with 3 DLBCL cases from individuals without HIV for comparison.

Results

Malignant B cells in HAL consistently exhibited high proliferative and oxidative phosphorylation (OXPHOS)-type metabolic signatures. Moreover, these cells demonstrated loss expression of major histocompatibility complex class I (MHC-I), strategically reducing tumor immunogenicity. HAL harbors special populations of naive and atypical memory B cells that exhibited high metabolic and immune-activated transcriptional profiles. Additionally, HAL exhibited senescence-like dysfunction in T cells, characterized by the reductions in regulatory activity of Treg and cytotoxic activity of CD8⁺ T cells, as well as decreases expression of IL7R genes and increases expression of FOS and FOSB genes. Our immunofluorescence results showed that the cytotoxic CD8⁺ T cells in HAL may have a dysfunction of lytic granule polarization. Furthermore, macrophages from HAL exhibited stronger immunosuppressive transcriptional characteristics, and a robust immunosuppressive SPP1-CD44 interaction was predicted between C1QA⁺ macrophages and T cells.

Conclusions

Our findings clearly indicate that HAL differs significantly from non-HAL, ranging from malignant B cells to the immune microenvironment. This study provides a comprehensive single-cell atlas of HIV-associated aggressive B-cell lymphomas, offering new insights into aggressiveness and immune evasion observed in HAL.

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hiv相关侵袭性b细胞淋巴瘤的单细胞免疫景观

人类免疫缺陷病毒（HIV）相关淋巴瘤（HAL），主要是侵袭性b细胞淋巴瘤，由于其多方面的发病机制和侵袭性的临床过程，在癌症研究中构成了重大挑战。尽管具有临床重要性，但这些淋巴瘤的基因组和免疫特征仍不清楚。方法采用单细胞RNA测序（scRNA-seq）方法对来自HIV感染者（PLWH）的6例弥漫性大b细胞淋巴瘤（DLBCL）和5例Burkitt淋巴瘤（BL）的侵袭性b细胞淋巴瘤淋巴结样本进行分析，并与来自非HIV感染者（PLWH）的3例DLBCL进行比较。结果HAL的恶性B细胞一致表现出高增殖和氧化磷酸化（OXPHOS）型代谢特征。此外，这些细胞表现出主要组织相容性复合体I类（MHC-I）的表达缺失，战略性地降低了肿瘤的免疫原性。HAL含有特殊的幼稚和非典型记忆B细胞群，它们表现出高代谢和免疫激活的转录谱。此外，HAL在T细胞中表现出衰老样功能障碍，其特征是Treg调控活性和CD8+ T细胞细胞毒活性降低，IL7R基因表达降低，FOS和FOSB基因表达增加。我们的免疫荧光结果显示，HAL的细胞毒性CD8+ T细胞可能存在溶解颗粒极化功能障碍。此外，HAL巨噬细胞表现出更强的免疫抑制转录特征，并且预测C1QA+巨噬细胞与T细胞之间存在强大的免疫抑制SPP1-CD44相互作用。结论从恶性B细胞到免疫微环境，HAL明显不同于非HAL。这项研究提供了hiv相关侵袭性b细胞淋巴瘤的全面单细胞图谱，为HAL观察到的侵袭性和免疫逃避提供了新的见解。

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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