CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Unveiling Extramedullary Myeloma Immune Microenvironment: A Systematic Review.
Unveiling Extramedullary Myeloma Immune Microenvironment: A Systematic Review.
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对微环境与骨髓瘤细胞相互作用的认识对于设计特异性治疗策略和改善疾病预后至关重要。
近年来，科学界为阐明肿瘤内克隆扩增和选择的内在机制所做的努力，促成了“肿瘤生态系统”理论的提出，该理论涉及微环境在治疗耐药和肿瘤进展中的作用等因素。在此背景下，微环境在多发性骨髓瘤（MM）发生发展中的贡献正受到研究，其中持续克隆演化备受强调。这一过程产生具有向髓外部位扩散潜能的侵袭性克隆，使任何治疗策略几乎无效。本系统综述旨在汇集关于髓外浆细胞骨髓瘤免疫微环境（IME）以及髓内与髓外疾病（EMD）之间免疫合成差异的知识。
根据PRISMA指南，在七个数据库中进行了检索策略，研究共纳入六篇符合纳入标准的文章。
分子分析、流式细胞术和免疫荧光获得的结果表明，EMD 部位存在显著的遗传不稳定性，同时 IME 具有空间和时间异质性，提示两者之间可能存在相关性。与髓内疾病相比，EMD 中的遗传和微环境变异性均显著更大。免疫抑制性微环境的建立是普遍规律，耗竭的 CD8+ 和自然杀伤（NK）细胞、M2 巨噬细胞和失活的树突状细胞被发现与肿瘤性浆细胞共定位，而细胞毒性 CD8+ 细胞、M1 巨噬细胞和活性树突状细胞则聚集在无肿瘤区域。还观察到治疗后免疫环境的改变，主要涉及 Tregs 和 MDSCs 的比例。
A search strategy according to PRISMA guidelines was conducted in seven databases, and six articles meeting the inclusion criteria were encompassed in the study.
Results obtained from molecular analysis as well as flow cytometry and immunofluorescence indicated profound genetic instability at EMD sites along with spatial and temporal heterogeneity of the IME, implying a possible correlation between them. Both genetic and microenvironment variability were notably greater in EMD compared to medullary disease. The establishment of an immunosuppressive microenvironment was the rule, with exhausted CD8+ and natural killer (NK) cells, M2 macrophages, and inactivated dendritic cells found co-localized with neoplastic plasma cells, whereas cytotoxic CD8+ cells, M1 macrophages, and active dendritic cells congregated in tumor-free areas. Post-therapy alterations in the immune milieu were also noted and were concerned mostly the percentages of Tregs and MDSCs.
The recognition of the microenvironment-myeloma cell interplay is essential for designing specific therapeutic strategies and ameliorating disease prognosis.
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