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Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire.

作者信息

Cheloni Giulia, Karagkouni Dimitra, Pita-Juarez Yered, Torres Daniela, Kanata Eleni, Liegel Jessica, Avigan Zachary, Saldarriaga Isabella, Chedid Georges, Rallis Kathrine, Miles Brodie, Tiwari Gayatri, Kim Jenny, Mattie Mike, Rosenblatt Jacalyn, Vlachos Ioannis S, Avigan David

机构信息

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA, USA.

出版信息

Nat Commun. 2025 May 23;16(1):4819. doi: 10.1038/s41467-025-59904-x.


DOI:10.1038/s41467-025-59904-x
PMID:40410132
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12102275/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/bf1b12248fb4/41467_2025_59904_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/f8531c24d42f/41467_2025_59904_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/9da42f8b2e35/41467_2025_59904_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/db1e0d68de28/41467_2025_59904_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/045aa8dd636a/41467_2025_59904_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/977930edf7c8/41467_2025_59904_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/88a433fc96ad/41467_2025_59904_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/bf1b12248fb4/41467_2025_59904_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/f8531c24d42f/41467_2025_59904_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/9da42f8b2e35/41467_2025_59904_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/db1e0d68de28/41467_2025_59904_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/045aa8dd636a/41467_2025_59904_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/977930edf7c8/41467_2025_59904_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/88a433fc96ad/41467_2025_59904_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/12102275/bf1b12248fb4/41467_2025_59904_Fig7_HTML.jpg

相似文献

[1]
Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire.

Nat Commun. 2025-5-23

[2]
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[3]
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[4]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

Genome Biol. 2025-3-14

[2]
C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer.

Nat Commun. 2024-5-27

[3]
CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity.

Blood Adv. 2024-6-25

[4]
Mitochondrial immune regulation and anti-tumor immunotherapy strategies targeting mitochondria.

Cancer Lett. 2023-6-28

[5]
NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.

Front Immunol. 2023

[6]
Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma.

Blood. 2023-5-11

[7]
TIMP-1 is a novel ligand of Amyloid Precursor Protein and triggers a proinflammatory phenotype in human monocytes.

J Cell Biol. 2023-2-6

[8]
Post-infusion CAR T cells identify patients resistant to CD19-CAR therapy.

Nat Med. 2022-9

[9]
Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma.

Nat Med. 2022-9

[10]
Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma.

Nat Med. 2022-9

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