Distinct cellular dynamics following CD19 and CD7 CAR-T therapies revealed by high-dimensional CyTOF analysis and impact on clinical outcomes
- 1Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Beijing, China.
- 2Peking-Tsinghua Center for Life Sciences, Beijing, China.
Abstract
Background and objectives
CD7 and CD19 chimeric antigen receptor T-cell (CAR-T) therapies induce high remission in T-cell acute lymphoblastic leukemia; however, clinical outcomes of CD7 CAR-T therapy are less favorable compared with those of CD19 CAR-T therapy due to profound immune dysfunction, elevated infection, and non-relapse mortality (NRM). Whether these differences arise from distinct immune remodeling patterns that shape CAR-T cell persistence, functional fitness, and host immune recovery, remains unknown.Methods
We analyzed 74 patients (52 CD19; 22 CD7) who received CAR-T therapy. A subset of 28 patients underwent prospective immune monitoring with 107 longitudinal samples profiled using 40-marker cytometry by time-of-flight to assess CAR-T cell kinetics, exhaustion, host immune remodeling, and clinical associations.Results
High-dimensional profiling revealed strikingly divergent immune trajectories of CD19 and CD7 CAR-T therapies. At day 28, CD7 CAR-T recipients exhibited diminished CD8 ⁺ CAR-T cell frequencies, early CAR-T cell exhaustion, and poor immune reconstitution, features more frequent among patients experiencing NRM. In contrast, CD19 CAR-T recipients showed sustained activation, low exhaustion, and prolonged persistence. These immunologic disparities translated into clinically meaningful differences where day-28 responses remained comparable (88.5% vs. 90.9%); however, CD7 CAR-T recipients developed higher late hematotoxicity and fatal infections, resulting in greater 1-year NRM (32.4% vs. 9.2%) and inferior overall survival (44.6% vs. 78.8%).Conclusion
CD7 and CD19 CAR-T therapies are associated with distinct patterns of immune remodeling and clinical outcomes. Compared with CD19 CAR-T therapy, CD7 CAR-T therapy was characterized by reduced CD8+ CAR-T persistence, early exhaustion, and delayed immune reconstitution, correlating with increased infections and higher non-relapse mortality.
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BibTeX
@article{zhou2026distinct,
title = {{Distinct cellular dynamics following CD19 and CD7 CAR-T therapies revealed by high-dimensional CyTOF analysis and impact on clinical outcomes}},
author = {Zhipeng Zhou and Yiyang Ding and Zhuojun Liu and Zhifan Zhao and Ting Zhao and Xiaohui Zhang and Xiaojun Huang and Meng Lyu and Xuying Pei and Xiangyu Zhao},
journal = {Journal of translational internal medicine},
year = {2026},
month = oct,
doi = {10.1515/jtim-2026-0081},
url = {https://europepmc.org/article/PMC/PMC13726658},
note = {CC BY},
}
RIS
TY - JOUR
TI - Distinct cellular dynamics following CD19 and CD7 CAR-T therapies revealed by high-dimensional CyTOF analysis and impact on clinical outcomes
AU - Zhipeng Zhou
AU - Yiyang Ding
AU - Zhuojun Liu
AU - Zhifan Zhao
AU - Ting Zhao
AU - Xiaohui Zhang
AU - Xiaojun Huang
AU - Meng Lyu
AU - Xuying Pei
AU - Xiangyu Zhao
PY - 2026
DA - 2026/10/23
JO - Journal of translational internal medicine
DO - 10.1515/jtim-2026-0081
UR - https://europepmc.org/article/PMC/PMC13726658
AB - Background and objectives CD7 and CD19 chimeric antigen receptor T-cell (CAR-T) therapies induce high remission in T-cell acute lymphoblastic leukemia; however, clinical outcomes of CD7 CAR-T therapy are less favorable compared with those of CD19 CAR-T therapy due to profound immune dysfunction, elevated infection, and non-relapse mortality (NRM). Whether these differences arise from distinct immune remodeling patterns that shape CAR-T cell persistence, functional fitness, and host immune recovery, remains unknown.Methods We analyzed 74 patients (52 CD19; 22 CD7) who received CAR-T therapy. A subset of 28 patients underwent prospective immune monitoring with 107 longitudinal samples profiled using 40-marker cytometry by time-of-flight to assess CAR-T cell kinetics, exhaustion, host immune remodeling, and clinical associations.Results High-dimensional profiling revealed strikingly divergent immune trajectories of CD19 and CD7 CAR-T therapies. At day 28, CD7 CAR-T recipients exhibited diminished CD8 ⁺ CAR-T cell frequencies, early CAR-T cell exhaustion, and poor immune reconstitution, features more frequent among patients experiencing NRM. In contrast, CD19 CAR-T recipients showed sustained activation, low exhaustion, and prolonged persistence. These immunologic disparities translated into clinically meaningful differences where day-28 responses remained comparable (88.5% vs. 90.9%); however, CD7 CAR-T recipients developed higher late hematotoxicity and fatal infections, resulting in greater 1-year NRM (32.4% vs. 9.2%) and inferior overall survival (44.6% vs. 78.8%).Conclusion CD7 and CD19 CAR-T therapies are associated with distinct patterns of immune remodeling and clinical outcomes. Compared with CD19 CAR-T therapy, CD7 CAR-T therapy was characterized by reduced CD8+ CAR-T persistence, early exhaustion, and delayed immune reconstitution, correlating with increased infections and higher non-relapse mortality.
SN - 2450-131X
SN - 2224-4018
ER -