Inflammatory Cytokines Shape an Altered Immune Response During Myeloid Malignancies.
Inflammatory Cytokines Shape an Altered Immune Response During Myeloid Malignancies.
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DOI：
10.3389/fimmu.2021.772408
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发表时间：
2021
影响因子：
7.3
通讯作者：
Welner RS
中科院分区：
文献类型：
--
作者：
Camacho V;Kuznetsova V;Welner RS
免疫微环境是白血病进展和血液病的关键驱动因素和调节因素。最近的研究表明，多种免疫成分在调节造血中起着核心作用，免疫细胞水平的功能障碍显著有助于肿瘤性疾病。免疫细胞对白血病炎性细胞因子暴露引起的重塑非常敏感。重要的是，免疫细胞是造血系统中的主要细胞因子生产者，代表了临床干预的未开发前沿。由于促炎细胞因子环境，免疫细胞状态的失调是血液病和肿瘤的标志。恶性免疫适应对白血病原始细胞增殖、疾病传播和耐药性具有深远影响。相反，靶向免疫景观以恢复造血功能并限制白血病扩展可能具有显著的治疗价值。尽管免疫微环境在血液病的发生、发展和治疗反应中起着重要作用，但缺乏对白血病细胞因子如何改变免疫细胞以允许、促进或抑制白血病生长的详细研究。在这里，我们概述了一个基于免疫的白血病转化模型，并强调了免疫改变对恶性肿瘤发展轨迹的深远影响。本综述的重点是总结目前的知识，促炎和抗炎细胞因子对免疫细胞亚群的影响，其作用方式，和免疫治疗的方法，有可能改善患有血液骨髓恶性肿瘤的患者的临床结果。
The immune microenvironment is a critical driver and regulator of leukemic progression and hematological disease. Recent investigations have demonstrated that multiple immune components play a central role in regulating hematopoiesis, and dysfunction at the immune cell level significantly contributes to neoplastic disease. Immune cells are acutely sensitive to remodeling by leukemic inflammatory cytokine exposure. Importantly, immune cells are the principal cytokine producers in the hematopoietic system, representing an untapped frontier for clinical interventions. Due to a proinflammatory cytokine environment, dysregulation of immune cell states is a hallmark of hematological disease and neoplasia. Malignant immune adaptations have profound effects on leukemic blast proliferation, disease propagation, and drug-resistance. Conversely, targeting the immune landscape to restore hematopoietic function and limit leukemic expansion may have significant therapeutic value. Despite the fundamental role of the immune microenvironment during the initiation, progression, and treatment response of hematological disease, a detailed examination of how leukemic cytokines alter immune cells to permit, promote, or inhibit leukemia growth is lacking. Here we outline an immune-based model of leukemic transformation and highlight how the profound effect of immune alterations on the trajectory of malignancy. The focus of this review is to summarize current knowledge about the impacts of pro- and anti-inflammatory cytokines on immune cells subsets, their modes of action, and immunotherapeutic approaches with the potential to improve clinical outcomes for patients suffering from hematological myeloid malignancies.