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
{"title":"hiv相关侵袭性b细胞淋巴瘤的单细胞免疫景观","authors":"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","doi":"10.1016/j.jncc.2025.02.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sup>+</sup> T cells, as well as decreases expression of <em>IL7R</em> genes and increases expression of <em>FOS</em> and <em>FOSB</em> genes. Our immunofluorescence results showed that the cytotoxic CD8<sup>+</sup> 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<sup>+</sup> macrophages and T cells.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 2","pages":"Pages 221-235"},"PeriodicalIF":7.6000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma\",\"authors\":\"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\",\"doi\":\"10.1016/j.jncc.2025.02.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sup>+</sup> T cells, as well as decreases expression of <em>IL7R</em> genes and increases expression of <em>FOS</em> and <em>FOSB</em> genes. Our immunofluorescence results showed that the cytotoxic CD8<sup>+</sup> 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<sup>+</sup> macrophages and T cells.</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":73987,\"journal\":{\"name\":\"Journal of the National Cancer Center\",\"volume\":\"5 2\",\"pages\":\"Pages 221-235\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the National Cancer Center\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667005425000213\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Cancer Center","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667005425000213","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma
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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