Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing
Abstract. Background:. Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to...
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| Language: | English |
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Wolters Kluwer
2025-08-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000003690 |
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| author | Xudong Li Hong Huang Fang Wang Mengjia Li Binglei Zhang Jianxiang Shi Yuke Liu Mengya Gao Mingxia Sun Haixia Cao Danfeng Zhang Na Shen Weijie Cao Zhilei Bian Haizhou Xing Wei Li Linping Xu Shiyu Zuo Yongping Song Tingting Yang Xiuyuan Hao |
| author_facet | Xudong Li Hong Huang Fang Wang Mengjia Li Binglei Zhang Jianxiang Shi Yuke Liu Mengya Gao Mingxia Sun Haixia Cao Danfeng Zhang Na Shen Weijie Cao Zhilei Bian Haizhou Xing Wei Li Linping Xu Shiyu Zuo Yongping Song Tingting Yang Xiuyuan Hao |
| author_sort | Xudong Li |
| collection | DOAJ |
| description | Abstract.
Background:. Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.
Methods:. In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45+ BM cells were enriched with human CD45 microbeads. The CD45+ cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.
Results:. In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.
Conclusions:. This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment. |
| format | Article |
| id | doaj-art-a152dcf7ee0c4a4ca548a05031777efe |
| institution | DOAJ |
| issn | 0366-6999 2542-5641 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj-art-a152dcf7ee0c4a4ca548a05031777efe2025-08-20T03:01:41ZengWolters KluwerChinese Medical Journal0366-69992542-56412025-08-01138151866188110.1097/CM9.0000000000003690202508050-00010Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencingXudong Li0Hong Huang1Fang Wang2Mengjia Li3Binglei Zhang4Jianxiang Shi5Yuke Liu6Mengya Gao7Mingxia Sun8Haixia Cao9Danfeng Zhang10Na Shen11Weijie Cao12Zhilei Bian13Haizhou Xing14Wei Li15Linping Xu16Shiyu Zuo17Yongping Song18Tingting YangXiuyuan Hao1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China3 BGI College & Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan 450052, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China4 Department of Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, China5 School of Public Health, Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China4 Department of Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China1 Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, ChinaAbstract. Background:. Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. Methods:. In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45+ BM cells were enriched with human CD45 microbeads. The CD45+ cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. Results:. In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. Conclusions:. This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.http://journals.lww.com/10.1097/CM9.0000000000003690 |
| spellingShingle | Xudong Li Hong Huang Fang Wang Mengjia Li Binglei Zhang Jianxiang Shi Yuke Liu Mengya Gao Mingxia Sun Haixia Cao Danfeng Zhang Na Shen Weijie Cao Zhilei Bian Haizhou Xing Wei Li Linping Xu Shiyu Zuo Yongping Song Tingting Yang Xiuyuan Hao Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing Chinese Medical Journal |
| title | Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing |
| title_full | Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing |
| title_fullStr | Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing |
| title_full_unstemmed | Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing |
| title_short | Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing |
| title_sort | decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large b cell lymphoma with cd19 car t failure by single cell rna sequencing |
| url | http://journals.lww.com/10.1097/CM9.0000000000003690 |
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