Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy.
Clin Cancer Res
; 30(18): 4201-4214, 2024 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-39024031
ABSTRACT
PURPOSE:
The purpose of this study was to investigate the remodeling of the multiple myeloma microenvironment after B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (CAR-T) cell therapy. EXPERIMENTALDESIGN:
We performed single-cell RNA sequencing on paired bone marrow specimens (n = 14) from seven patients with multiple myeloma before (i.e., baseline, "day -4") and after (i.e., "day 28") lymphodepleted BCMA CAR-T cell therapy.RESULTS:
Our analysis revealed heterogeneity in gene expression profiles among multiple myeloma cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells, enhanced CD8+ effector T-cell cytotoxic activity, and elevated type 1 conventional dendritic cell (DC) antigen presentation ability. DC re-clustering inferred intramedullary-originated type 3 conventional DCs with extramedullary migration. Cell-cell communication network analysis indicated that BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-multiple myeloma immunity.CONCLUSIONS:
Our study sheds light on multiple myeloma microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.
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Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
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Antígeno de Maturação de Linfócitos B
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Microambiente Tumoral
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Receptores de Antígenos Quiméricos
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Mieloma Múltiplo
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article