Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma
Abstract B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients...
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| Format: | Article |
| Language: | English |
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Springer
2025-01-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01810-1 |
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| author | Ying Ni Qun Zhang Xiaochen Tang Xiuchun Li Shiguang Ye Yan Lu Aibin Liang Ping Li |
| author_facet | Ying Ni Qun Zhang Xiaochen Tang Xiuchun Li Shiguang Ye Yan Lu Aibin Liang Ping Li |
| author_sort | Ying Ni |
| collection | DOAJ |
| description | Abstract B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment. We found that low concentrations of chidamide did not enhance the ability of CD19 CAR T cells to kill B-NHL cells during and after preparation. B-NHL cells pretreated with chidamide were more likely to be killed by CD19 CAR T cells. CD19 CAR T cells secreted more cytokines (IL-2, TNF-α, and IFN-γ) after co-culture with B-NHL cells pretreated with chidamide. At the same time, the expression of CD19 on B-NHL cell surface was increased by chidamide. In vivo experiments showed that infusion of CD19 CAR T cells after chidamide bridging intervention can enhance the therapeutic effect of B-NHL and prolong the overall survival of mice. This study provides a new direction and theoretical foundation for CD19 CAR T cell therapy in B-NHL. |
| format | Article |
| id | doaj-art-63bf8e76814a44188308b527d3eceeaf |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-63bf8e76814a44188308b527d3eceeaf2025-01-26T12:39:56ZengSpringerDiscover Oncology2730-60112025-01-0116111310.1007/s12672-025-01810-1Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphomaYing Ni0Qun Zhang1Xiaochen Tang2Xiuchun Li3Shiguang Ye4Yan Lu5Aibin Liang6Ping Li7Department of Hematology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineAbstract B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment. We found that low concentrations of chidamide did not enhance the ability of CD19 CAR T cells to kill B-NHL cells during and after preparation. B-NHL cells pretreated with chidamide were more likely to be killed by CD19 CAR T cells. CD19 CAR T cells secreted more cytokines (IL-2, TNF-α, and IFN-γ) after co-culture with B-NHL cells pretreated with chidamide. At the same time, the expression of CD19 on B-NHL cell surface was increased by chidamide. In vivo experiments showed that infusion of CD19 CAR T cells after chidamide bridging intervention can enhance the therapeutic effect of B-NHL and prolong the overall survival of mice. This study provides a new direction and theoretical foundation for CD19 CAR T cell therapy in B-NHL.https://doi.org/10.1007/s12672-025-01810-1B-cell non-Hodgkin lymphomaCD19 CAR TChidamide |
| spellingShingle | Ying Ni Qun Zhang Xiaochen Tang Xiuchun Li Shiguang Ye Yan Lu Aibin Liang Ping Li Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma Discover Oncology B-cell non-Hodgkin lymphoma CD19 CAR T Chidamide |
| title | Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma |
| title_full | Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma |
| title_fullStr | Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma |
| title_full_unstemmed | Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma |
| title_short | Upregulation of CD19 by low‐dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma |
| title_sort | upregulation of cd19 by low dose chidamide promotes car t cells functionality in b cell non hodgkin lymphoma |
| topic | B-cell non-Hodgkin lymphoma CD19 CAR T Chidamide |
| url | https://doi.org/10.1007/s12672-025-01810-1 |
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