Scholarlink

<p>Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and presents major therapeutic challenges due to its intrinsic heterogeneity and frequent development of resistance to immunotherapy. Although recent advances in immunotherapeutic strategies, including immunomodulatory drugs (IMiDs), chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and bispecific antibodies (BsAbs), have significantly improved patient outcomes, disease relapse remains nearly inevitable. This review systematically categorizes resistance mechanisms to immunotherapy in MM by examining intrinsic tumor cell factors, including genetic and epigenetic alterations, modulation or loss of target antigens, immune effector cell dysfunction such as T-cell exhaustion, and the complex suppressive features of the bone marrow microenvironment. In addition, we discuss the application of emerging technologies such as single-cell sequencing and CRISPR/Cas9-based functional screening to uncover resistance pathways and guide target discovery. Finally, we highlight rational strategies to overcome resistance, including synergistic combination regimens, development of next-generation therapeutics, and approaches to reprogram the tumor microenvironment. These insights provide a conceptual framework for the design of more effective and durable immunotherapeutic interventions in MM.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance

  • 期刊论文

  • 发表日期：

    2026年4月28日

查看全文
  • Huan Li,
  • Qi Xia,
  • Mei Yu,
  • Ying Lv,
  • Jialing Xiao,
  • Xiaoxin Guo,
  • Kai Dong,
  • Yu Zhou,
  • Ling Zhong,
  • Ting Wang,
  • Weijia Wu,
  • Chengzi Gan,
  • Mingze Li,
  • Ning Xiao,
  • Qiang Wang,
  • Hong Chang,
  • Yu He,
  • Bo Gong

摘要

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and presents major therapeutic challenges due to its intrinsic heterogeneity and frequent development of resistance to immunotherapy. Although recent advances in immunotherapeutic strategies, including immunomodulatory drugs (IMiDs), chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and bispecific antibodies (BsAbs), have significantly improved patient outcomes, disease relapse remains nearly inevitable. This review systematically categorizes resistance mechanisms to immunotherapy in MM by examining intrinsic tumor cell factors, including genetic and epigenetic alterations, modulation or loss of target antigens, immune effector cell dysfunction such as T-cell exhaustion, and the complex suppressive features of the bone marrow microenvironment. In addition, we discuss the application of emerging technologies such as single-cell sequencing and CRISPR/Cas9-based functional screening to uncover resistance pathways and guide target discovery. Finally, we highlight rational strategies to overcome resistance, including synergistic combination regimens, development of next-generation therapeutics, and approaches to reprogram the tumor microenvironment. These insights provide a conceptual framework for the design of more effective and durable immunotherapeutic interventions in MM.