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<p>Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy characterized by significant immune evasion mechanisms. Its immune microenvironment comprises various immune cells, including dendritic cells (DCs), natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immunosuppressive factors such as TGF-β and IL-10, which collectively inhibit immune responses. Dysfunctional DCs, impaired NK cell activity and the immunosuppressive effects of MDSCs and Tregs foster tumor cell immune evasion, thereby limiting the efficacy of immunotherapies. In recent years, significant advancements in MM treatment have come from immunotherapy: monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) have emerged as key strategies for improving patient outcomes. However, variability in therapeutic efficacy, treatment-related toxicity and the development of resistance remain major obstacles in clinical practice. The MM immune microenvironment, together with tumor cell heterogeneity, complicates treatment and restricts the widespread application and long-term effectiveness of current therapies. To address these challenges, researchers are exploring novel therapeutic targets and integrating gene-editing technologies with immunotherapy to enhance efficacy. The rise of precision medicine and personalized treatment approaches offers further opportunities to optimize therapeutic strategies. Continued progress in MM immunotherapy depends on close collaboration among academia, healthcare institutions, industry and policymakers. Through interdisciplinary cooperation and resource integration, current obstacles can be overcome, accelerating the development and clinical translation of innovative therapies and ultimately providing safer, more effective treatment options for patients.</p>

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Immunotherapy in multiple myeloma: advances from immune microenvironment insights to clinical application

  • 期刊论文

  • 发表日期：

    2025年12月3日

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  • Yao Zhang,
  • Yuting Lei,
  • Yanzhao Huang,
  • Yan Gao,
  • Rong Liu,
  • Kaiyun Guo,
  • Chunlian Zhao,
  • Ming Lei

摘要

Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy characterized by significant immune evasion mechanisms. Its immune microenvironment comprises various immune cells, including dendritic cells (DCs), natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immunosuppressive factors such as TGF-β and IL-10, which collectively inhibit immune responses. Dysfunctional DCs, impaired NK cell activity and the immunosuppressive effects of MDSCs and Tregs foster tumor cell immune evasion, thereby limiting the efficacy of immunotherapies. In recent years, significant advancements in MM treatment have come from immunotherapy: monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) have emerged as key strategies for improving patient outcomes. However, variability in therapeutic efficacy, treatment-related toxicity and the development of resistance remain major obstacles in clinical practice. The MM immune microenvironment, together with tumor cell heterogeneity, complicates treatment and restricts the widespread application and long-term effectiveness of current therapies. To address these challenges, researchers are exploring novel therapeutic targets and integrating gene-editing technologies with immunotherapy to enhance efficacy. The rise of precision medicine and personalized treatment approaches offers further opportunities to optimize therapeutic strategies. Continued progress in MM immunotherapy depends on close collaboration among academia, healthcare institutions, industry and policymakers. Through interdisciplinary cooperation and resource integration, current obstacles can be overcome, accelerating the development and clinical translation of innovative therapies and ultimately providing safer, more effective treatment options for patients.