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多发性骨髓瘤的免疫治疗:从免疫微环境认识到临床应用的进展

英文原题:Immunotherapy in multiple myeloma: advances from immune microenvironment insights to clinical application.

查看英文原题

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

PubMed 2025/12/03(内容时间) Mol Biol Rep Q3 · IF 3.2(JCR 2025)

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中文摘要

多发性骨髓瘤(MM)是一种高度异质性的浆细胞恶性肿瘤,以显著的免疫逃逸机制为特征。其免疫微环境由多种免疫细胞组成,包括树突状细胞(DCs)、自然杀伤(NK)细胞、髓源性抑制细胞(MDSCs)和调节性T细胞(Tregs),以及TGF-和IL-10等免疫抑制因子,它们共同抑制免疫反应。DCs功能失调、NK细胞活性受损以及MDSCs和Tregs的免疫抑制作用促进肿瘤细胞免疫逃逸,从而限制了免疫治疗的疗效。近年来,MM治疗的重大进展来自免疫治疗:单克隆抗体、CAR-T 细胞疗法和双特异性抗体(BsAbs)已成为改善患者预后的关键策略。

然而,疗效的变异性、治疗相关毒性以及耐药性的产生仍然是临床实践中的主要障碍。MM免疫微环境连同肿瘤细胞异质性,使治疗复杂化,并限制了当前疗法的广泛应用和长期有效性。为应对这些挑战,研究人员正在探索新的治疗靶点,并将基因编辑技术与免疫治疗相结合以提高疗效。精准医学和个体化治疗方法的兴起为进一步优化治疗策略提供了机会。MM免疫治疗的持续进展依赖于学术界、医疗机构、产业界和政策制定者之间的密切合作。通过跨学科合作和资源整合,可以克服当前障碍,加速创新疗法的开发和临床转化,最终为患者提供更安全、更有效的治疗选择。

展开英文摘要原文

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- 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.

论文信息

作者
Zhang Y、Lei Y、Huang Y、Gao Y、Liu R、Guo K、Zhao C、Lei M
第一作者单位
Department of Medical Laboratory Section, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Located at 818 Renmin Road, Wuling, Changde, Hunan Province, China.China
通讯作者单位
Department of Medical Laboratory Section, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Located at 818 Renmin Road, Wuling, Changde, Hunan Province, China. 285928388@csu.edu.cn.China
文献类型
综述
期刊
Molecular biology reports2025 Dec 3
原文标识
PubMed 41335261 · DOI 10.1007/s11033-025-11317-1