Research Article: Multi-omics reveals immune features in immune and non-immune cells, an IFN-?/IFN-?-B2M positive feedback loop, and targeted metabolic therapy in multiple myeloma
Abstract:
Multiple myeloma (MM) is highly heterogeneous, with relapse occurring in the majority of cases, and recent advancements in single-cell RNA sequencing (scRNA-seq), sc-metabolism profiling, and bulk RNA-seq have facilitated the identification of cell subpopulations and metabolic reprogramming at the single-cell level, uncovering novel molecular mechanisms. This study aims to establish a multi-omics atlas of MM, characterizing the cell subpopulations and signaling pathways that drive immune evasion and disease progression. Additionally, sc-metabolic profiling identifies reprogramming patterns and informs therapeutic screening. We integrated scRNA-seq and bulk RNA-seq data using R to analyze immune and non-immune cell features and pathways in MM. Metabolic reprogramming was assessed via sc-metabolic profiling, and drug candidates were screened through multi-omics integration, with efficacy evaluated in vitro using CCK-8 assays, flow cytometry, Western blotting, and CalcuSyn software. Novel MM subpopulations were identified, including myeloma-activated hematopoietic stem cells and ISG15+ B cells, which correlated with survival and were validated by multiplex immunofluorescence. IFN-? is primarily secreted by effector memory CD8+T cells, and IFN-? is primarily secreted by non-classical monocytes, driving an IFN-?/?-B2M feedback loop. Multi-omics identified four drug candidates, each demonstrating anti-tumor effects against myeloma cell lines.
Introduction:
Multiple myeloma (MM) remains an incurable malignancy with a high risk of recurrence, despite advancements in therapeutic strategies ( 1 , 2 ). Current treatments, including proteasome inhibitors, immunomodulatory regimens, and haematopoietic cell transplants, have led to significant improvements in patient outcomes. However, challenges such as relapse, drug resistance, and treatment-associated toxicity continue to limit long-term efficacy ( 1 – 3 ). Consequently, a deeper understanding of the tumor…
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