CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Advances in immune microenvironment profiling during multiple myeloma progression and therapy.
Advances in immune microenvironment profiling during multiple myeloma progression and therapy.
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近期治疗进展，包括免疫调节药物、蛋白酶体抑制剂、单克隆抗体、双特异性抗体和CAR-T 细胞疗法，已改变了多发性骨髓瘤（MM）的治疗格局。除直接细胞毒性外，这些药物深刻重塑了骨髓免疫微环境，而该微环境在疾病发生、进展和治疗反应中起决定性作用。MM细胞通过招募和重编程调节性T细胞、髓源性抑制细胞、树突状细胞和巨噬细胞，在这一特殊生态位中旺盛生长，从而抑制抗肿瘤免疫，同时驱动效应T细胞功能性耗竭并损害NK 细胞毒性。越来越多的证据表明，这些免疫改变甚至在前驱阶段，如意义未明的单克隆丙种球蛋白病和冒烟型MM中就已出现，并随疾病演变而逐渐加剧。在本综述中，我们综合了关于MM进展过程中免疫细胞动态的最新见解，重点关注调节性和效应性细胞区室。
我们进一步讨论了当代疗法如何调节这些免疫相互作用，强调其在促进免疫激活的同时，有时维持免疫抑制通路的双重作用。全面理解MM中的免疫格局对于优化现有治疗、克服治疗耐药和指导下一代免疫疗法的开发至关重要。
Recent therapeutic advances, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor-T-cell therapies, have transformed the treatment landscape of multiple myeloma (MM). Beyond direct cytotoxicity, these agents profoundly reshape the bone marrow immune microenvironment, which plays a decisive role in disease initiation, progression, and therapeutic response.
MM cells thrive within this specialized niche by recruiting and reprogramming regulatory T cells, myeloid-derived suppressor cells, dendritic cells, and macrophages to suppress antitumor immunity while simultaneously driving functional exhaustion of effector T cells and impairing natural killer cell cytotoxicity.
Accumulating evidence demonstrates that these immune alterations emerge even at precursor stages, such as monoclonal gammopathy of undetermined significance and smoldering MM, progressively intensifying disease evolution. In this review, we synthesize recent insights into immune cell dynamics during MM progression, highlighting both regulatory and effector compartments.
We further discuss how contemporary therapies modulate these immune interactions, underscoring their dual roles in fostering immune activation while, at times, sustaining immunosuppressive pathways. A comprehensive understanding of the immune landscape in MM will be critical to optimizing existing treatments, overcoming therapeutic resistance, and guiding the development of next-generation immunotherapies.
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