Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire
Abstract While Chimeric Antigen Receptor (CAR) T cell therapy may result in durable remissions in recurrent large B cell lymphoma, persistence is limited and the mechanisms underlying long-term response are not fully elucidated. Using longitudinal single-cell immunoprofiling, here we compare the imm...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59904-x |
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| author | Giulia Cheloni Dimitra Karagkouni Yered Pita-Juarez Daniela Torres Eleni Kanata Jessica Liegel Zachary Avigan Isabella Saldarriaga Georges Chedid Kathrine Rallis Brodie Miles Gayatri Tiwari Jenny Kim Mike Mattie Jacalyn Rosenblatt Ioannis S. Vlachos David Avigan |
| author_facet | Giulia Cheloni Dimitra Karagkouni Yered Pita-Juarez Daniela Torres Eleni Kanata Jessica Liegel Zachary Avigan Isabella Saldarriaga Georges Chedid Kathrine Rallis Brodie Miles Gayatri Tiwari Jenny Kim Mike Mattie Jacalyn Rosenblatt Ioannis S. Vlachos David Avigan |
| author_sort | Giulia Cheloni |
| collection | DOAJ |
| description | Abstract While Chimeric Antigen Receptor (CAR) T cell therapy may result in durable remissions in recurrent large B cell lymphoma, persistence is limited and the mechanisms underlying long-term response are not fully elucidated. Using longitudinal single-cell immunoprofiling, here we compare the immune landscape in durable remission versus early relapse patients following CD19 CAR T cell infusion in the NCT02348216 (ZUMA-1) trial. Four weeks post-infusion, both cohorts demonstrate low circulating CAR T cells. We observe that long-term remission is associated with elevated native cytotoxic and proinflammatory effector cells, and post-infusion clonotypic expansion of effector memory T cells. Conversely, early relapse is associated with impaired NK cell cytotoxicity and elevated immunoregulatory cells, potentially dampening native T cell activation. Thus, we suggest that durable remission to CAR T is associated with a distinct T cell signature and pattern of clonotypic expansion within the native T cell compartment post-therapy, consistent with their contribution to the maintenance of response. |
| format | Article |
| id | doaj-art-4985eb72b6f44f3ebb757d72d569f9d1 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4985eb72b6f44f3ebb757d72d569f9d12025-08-20T03:08:43ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59904-xDurable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoireGiulia Cheloni0Dimitra Karagkouni1Yered Pita-Juarez2Daniela Torres3Eleni Kanata4Jessica Liegel5Zachary Avigan6Isabella Saldarriaga7Georges Chedid8Kathrine Rallis9Brodie Miles10Gayatri Tiwari11Jenny Kim12Mike Mattie13Jacalyn Rosenblatt14Ioannis S. Vlachos15David Avigan16Department of Medicine, Beth Israel Deaconess Medical CenterCancer Center, Beth Israel Deaconess Medical CenterCancer Center, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterDepartment of Pathology, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterKite, a Gilead CompanyKite, a Gilead CompanyKite, a Gilead CompanyKite, a Gilead CompanyDepartment of Medicine, Beth Israel Deaconess Medical CenterCancer Center, Beth Israel Deaconess Medical CenterDepartment of Medicine, Beth Israel Deaconess Medical CenterAbstract While Chimeric Antigen Receptor (CAR) T cell therapy may result in durable remissions in recurrent large B cell lymphoma, persistence is limited and the mechanisms underlying long-term response are not fully elucidated. Using longitudinal single-cell immunoprofiling, here we compare the immune landscape in durable remission versus early relapse patients following CD19 CAR T cell infusion in the NCT02348216 (ZUMA-1) trial. Four weeks post-infusion, both cohorts demonstrate low circulating CAR T cells. We observe that long-term remission is associated with elevated native cytotoxic and proinflammatory effector cells, and post-infusion clonotypic expansion of effector memory T cells. Conversely, early relapse is associated with impaired NK cell cytotoxicity and elevated immunoregulatory cells, potentially dampening native T cell activation. Thus, we suggest that durable remission to CAR T is associated with a distinct T cell signature and pattern of clonotypic expansion within the native T cell compartment post-therapy, consistent with their contribution to the maintenance of response.https://doi.org/10.1038/s41467-025-59904-x |
| spellingShingle | Giulia Cheloni Dimitra Karagkouni Yered Pita-Juarez Daniela Torres Eleni Kanata Jessica Liegel Zachary Avigan Isabella Saldarriaga Georges Chedid Kathrine Rallis Brodie Miles Gayatri Tiwari Jenny Kim Mike Mattie Jacalyn Rosenblatt Ioannis S. Vlachos David Avigan Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire Nature Communications |
| title | Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire |
| title_full | Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire |
| title_fullStr | Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire |
| title_full_unstemmed | Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire |
| title_short | Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire |
| title_sort | durable response to car t is associated with elevated activation and clonotypic expansion of the cytotoxic native t cell repertoire |
| url | https://doi.org/10.1038/s41467-025-59904-x |
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