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.
10.1097/CM9.0000000000003690
- Author:
Xudong LI
1
;
Hong HUANG
1
;
Fang WANG
1
;
Mengjia LI
1
;
Binglei ZHANG
1
;
Jianxiang SHI
2
;
Yuke LIU
1
;
Mengya GAO
3
;
Mingxia SUN
4
;
Haixia CAO
1
;
Danfeng ZHANG
1
;
Na SHEN
1
;
Weijie CAO
1
;
Zhilei BIAN
1
;
Haizhou XING
1
;
Wei LI
1
;
Linping XU
3
;
Shiyu ZUO
1
;
Yongping SONG
1
Author Information
1. Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.
2. BGI College & Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan 450052, China.
3. Department of Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, China.
4. School of Public Health, Zhengzhou University, Zhengzhou, Henan 450000, China.
- Publication Type:Journal Article
- Keywords:
CD45;
Chimeric antigen receptor T;
Chronic myelomonocytic leukemia;
Diffuse large B cell lymphoma;
Immune microenvironment;
Secondary tumor;
Single-cell RNA sequencing
- MeSH:
Humans;
Lymphoma, Large B-Cell, Diffuse/therapy*;
Tumor Microenvironment/genetics*;
Antigens, CD19/metabolism*;
Leukemia, Myelomonocytic, Chronic/genetics*;
Immunotherapy, Adoptive/adverse effects*;
Male;
Single-Cell Analysis/methods*;
Female;
Sequence Analysis, RNA/methods*;
Receptors, Chimeric Antigen;
Middle Aged
- From:
Chinese Medical Journal
2025;138(15):1866-1881
- CountryChina
- Language:English
-
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.
