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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1575079

Multi-Omics Reveals Immune Featur es in Immune and Non-Immune Cells, an IFN-γ/IFN-α-B2M Positive Feedback Loop, and Tar geted Metabolic Ther apy in

Provisionally accepted
  • Fuyang People’s Hospital, Fuyang City, China

The final, formatted version of the article will be published soon.

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-γ is primarily secreted by effector memory CD8+T cells, and IFN-α is primarily secreted by non-classical monocytes, driving an IFN-γ/α-B2M feedback loop. Multi-omics identified four drug candidates, with CB839+EGCG as the most effective combination.

Keywords: Multiple Myeloma, multi-omics Atlas, non-immune cells, signaling pathway, metabolic reprogramming-targeted

Received: 11 Feb 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Li and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yuhu Feng, Fuyang People’s Hospital, Fuyang City, China

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