Zhang Xiaomei, Yang Zailin, Xie Xiaoqing, Li Jun, Xiao Qing, Xu Guofa, Ma Ben, Xie Xudong, Liu Yi, Zhai Liuyue, Tang Yifeng, Fu Huihui, He Sanxiu, Liu Tingting, Huang Dehong, Zeng Censi, Zhou Yixing, Hu Renzhi, Guo Binling, Wang Chaoyu, Liang Shunsi, Luo Qin, Lv Jing, Nan Yingyu, Li Jieping, Li Qiying, Wang Shengqiang, Wu Yongzhong, Liu Yao
Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, China.
Department of Hematology and Medical Oncology, Chongqing University Fuling Hospital, Chongqing, China.
J Natl Cancer Cent. 2025 Feb 12;5(2):221-235. doi: 10.1016/j.jncc.2025.02.001. eCollection 2025 Apr.
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.
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.
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 genes and increases expression of and 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.
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.
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病程，在癌症研究中构成了重大挑战。尽管其具有临床重要性，但这些淋巴瘤的基因组和免疫特征仍未得到充分阐明。
我们对侵袭性B细胞淋巴瘤的淋巴结样本进行了单细胞RNA测序（scRNA-seq），主要包括6例来自HIV感染者（PLWH）的弥漫性大B细胞淋巴瘤（DLBCL）和5例伯基特淋巴瘤（BL），以及3例来自未感染HIV个体的DLBCL病例作为对照。
HAL中的恶性B细胞始终表现出高增殖和氧化磷酸化（OXPHOS）型代谢特征。此外，这些细胞显示主要组织相容性复合体I类（MHC-I）的表达缺失，从而策略性地降低了肿瘤免疫原性。HAL含有特殊的幼稚和非典型记忆B细胞群体，这些细胞表现出高代谢和免疫激活的转录谱。此外，HAL在T细胞中表现出类似衰老的功能障碍，其特征是调节性T细胞（Treg）的调节活性和CD8 T细胞的细胞毒性活性降低，以及某些基因表达减少和其他基因表达增加。我们的免疫荧光结果表明，HAL中的细胞毒性CD8 T细胞可能存在溶细胞颗粒极化功能障碍。此外，HAL中的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性SPP1-CD44相互作用。
我们的研究结果清楚地表明，HAL与非HAL在从恶性B细胞到免疫微环境等方面存在显著差异。本研究提供了一份全面的HIV相关侵袭性B细胞淋巴瘤单细胞图谱，为HAL中观察到的侵袭性和免疫逃逸提供了新的见解。
