In vitro analysis reveals that therapy-induced senescence in myeloma cells leads to resistance to T-cell therapies, indicating potential treatment implications.
Key Points
To investigate the activation of therapy-induced senescence in myeloma cells and its link to resistance against T-cell directed therapies.
Integrated single-cell RNA sequencing data from multiple myeloma patients and healthy controls.
Evaluated senescence using scGSEA and established gene sets.
Conducted in vitro cytotoxicity assays with H929 myeloma cells treated with vehicle or high-dose melphalan.
Co-cultured treated myeloma cells with T cells to assess cytotoxicity.
Higher enrichment of senescence-related gene sets was found in late-stage myeloma cells compared to newly diagnosed cases.
Increased expression of senescence marker CDKN2A and myeloid markers in late-stage compared to early-stage myeloma cells.
H929HDM cells showed significantly reduced killing by CAR-T and teclistamab compared to control (p<0.05).
Baseline senescence markers inversely correlated with progression-free survival in patients receiving CAR-T therapy.