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Although depletion of target\u2010positive lymphocytes is expected, the contribution of residual cell dysfunction to infection risk remains unclear. This work uses single\u2010cell sequencing to investigate immune dysregulation after 5CAR or 7CAR therapy in patients with T\u2010cell acute lymphoblastic leukemia. 5CAR induces marked T\u2010cell exhaustion linked to CD5 loss and B lymphocyte\u2010induced maturation protein 1 upregulation. This is accompanied by reduced frequency and diversity of Epstein\u2010Barr virus (EBV)\u2010associated T\u2010cell receptors, potentially contributing to the high incidence of severe EBV infection. 5CAR therapy also impairs B\u2010cell function and diversity while enhancing natural killer cell function and monocyte activation. In contrast, 7CAR reduces the frequency and diversity of multiple pathogen\u2010associated T\u2010cell receptors, but causes less T\u2010cell exhaustion. 7CAR also substantially impairs innate immunity by decreasing monocyte activation and eliminating dendritic cells, which may contribute to the high risk of infection. Thus, unlike CD19 and CD22 CAR therapy, which primarily affects B cells, 5CAR and 7CAR therapies result in broad dysregulation across multiple immune cell types, providing a basis for infection prevention and safer CAR\u2010T therapy.<\/jats:p>","DOI":"10.1002\/advs.202509259","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T03:35:51Z","timestamp":1764128151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Dissection Reveals Immune Dysregulation After CD5 or CD7\u2010Directed Chimeric Antigen Receptor T\u2010Cell Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuechen","family":"Luo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin 300020 China"},{"name":"Tianjin Institutes of Health Science  Tianjin 301600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin 300020 China"},{"name":"Tianjin Institutes of Health Science  Tianjin 301600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiting","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin 300020 China"},{"name":"Tianjin Institutes of Health Science  Tianjin 301600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Wang","sequence":"additional","affiliation":[{"name":"Novogene Co., Ltd.  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