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 characteristic...
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Elsevier
2025-04-01
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| Series: | Journal of the National Cancer Center |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667005425000213 |
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| author | 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 Shunsi Liang Qin Luo Jing Lv Yingyu Nan Jieping Li Qiying Li Shengqiang Wang Yongzhong Wu Yao Liu |
| author_facet | 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 Shunsi Liang Qin Luo Jing Lv Yingyu Nan Jieping Li Qiying Li Shengqiang Wang Yongzhong Wu Yao Liu |
| author_sort | Xiaomei Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7ae40f3dd03a4c339646c81fe13eecc4 |
| institution | OA Journals |
| issn | 2667-0054 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the National Cancer Center |
| spelling | doaj-art-7ae40f3dd03a4c339646c81fe13eecc42025-08-20T02:16:02ZengElsevierJournal of the National Cancer Center2667-00542025-04-015222123510.1016/j.jncc.2025.02.001The single-cell immune landscape of HIV-associated aggressive B-cell lymphomaXiaomei Zhang0Zailin Yang1Xiaoqing Xie2Jun Li3Qing Xiao4Guofa Xu5Ben Ma6Xudong Xie7Yi Liu8Liuyue Zhai9Yifeng Tang10Huihui Fu11Sanxiu He12Tingting Liu13Dehong Huang14Censi Zeng15Yixing Zhou16Renzhi Hu17Binling Guo18Chaoyu Wang19Shunsi Liang20Qin Luo21Jing Lv22Yingyu Nan23Jieping Li24Qiying Li25Shengqiang Wang26Yongzhong Wu27Yao Liu28Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, China; Department of Hematology and Medical Oncology, Chongqing University Fuling Hospital, Chongqing, ChinaDepartment of Integrated, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Integrated, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, ChinaDepartment of Integrated, Chongqing University Cancer Hospital, Chongqing, China; Corresponding authors.Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China; Corresponding authors.Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2667005425000213HIV-associated lymphomasSingle-cell RNA sequencingDLBCL |
| spellingShingle | 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 Shunsi Liang Qin Luo Jing Lv Yingyu Nan Jieping Li Qiying Li Shengqiang Wang Yongzhong Wu Yao Liu The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma Journal of the National Cancer Center HIV-associated lymphomas Single-cell RNA sequencing DLBCL |
| title | The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma |
| title_full | The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma |
| title_fullStr | The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma |
| title_full_unstemmed | The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma |
| title_short | The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma |
| title_sort | single cell immune landscape of hiv associated aggressive b cell lymphoma |
| topic | HIV-associated lymphomas Single-cell RNA sequencing DLBCL |
| url | http://www.sciencedirect.com/science/article/pii/S2667005425000213 |
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