GEO series
CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy I
GSE246342
Homo sapiens
Expression profiling by high throughput sequencing; Other
18 samples
Submitted 2024/07/29
Platform GPL24676
Summary
Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occurs in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFβ. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.
Published in
Ledergor G, Fan Z, Wu K et al.
· Blood advances 2024
· PMID 38574299
· doi:10.1182/bloodadvances.2023012416
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE246342_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 18 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1032579 and SRA study SRP468635. Searching any of these in the dataset finder brings you back here.
Study design
18 conditions, each sampled once — no replicated groups
Supports a case/control comparison: 14 samples read as cases, 4 as controls.
Read from 18 sample titles: 18 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7867490 Myeloma_patient_01_T_cells, Gene expression (T1_GEX)
- GSM7867491 Myeloma_patient_01_T_cells, T cell receptor (T1_TCR)
- GSM7867492 Myeloma_patient_01_T_cells, Gene expression (T2_GEX)
- GSM7867493 Myeloma_patient_01_T_cells, T cell receptor (T2_TCR)
- GSM7867494 Myeloma_patient_02_T_cells, Gene expression (T3_GEX)
- GSM7867495 Myeloma_patient_02_T_cells, Surface protein (T3_CSFL)
- GSM7867496 Myeloma_patient_02_T_cells, T cell receptor (T3_TCR)
- GSM7867497 Myeloma_patient_03_T_cells, Gene expression (T4_GEX)
- GSM7867498 Myeloma_patient_03_T_cells, Surface protein (T4_CSFL)
- GSM7867499 Myeloma_patient_03_T_cells, T cell receptor (T4_TCR)
- GSM7867500 Myeloma_patient_04_T_cells, Gene expression (T5_GEX)
- GSM7867501 Myeloma_patient_04_T_cells, T cell receptor (T5_TCR)
- GSM7867502 Healthy_donor_01_T_cells, Gene expression (T42_GEX)
- GSM7867503 Healthy_donor_01_T_cells, T cell receptor (T42_TCR)
- GSM7867504 Healthy_donor_01_T_cells, Gene expression (T43_GEX)
- GSM7867505 Healthy_donor_01_T_cells, T cell receptor (T43_TCR)
- GSM7867506 Myeloma_patient_01_nonBnonT_cells, Gene expression (M1_GEX)
- GSM7867507 Myeloma_patient_01_nonBnonT_cells, Gene expression (M2_GEX)
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