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The Role of Regulatory T Cells and TH17 Cells in Multiple Myeloma

机译:调节性T细胞和TH17细胞在多发性骨髓瘤中的作用

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The development of multiple myeloma (MM) involves a series of genetic alterations and changes in the bone marrow microenvironment, favoring the growth of the tumor and failure of local immune control. Quantitative and functional alterations in CD4+and CD8+T cells have been described in MM. The balance between T regulatory cells (Treg) and T helper (Th) 17 cells represents one essential prerequisite for maintaining anti-tumor immunity in MM. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against infections and tumor cells. In MM patients, Tregs seem to contribute to myeloma-related immune dysfunction and targeting them could, therefore, help to restore and enhance vital immune responses. Th17 cells protect against fungal and parasitic infections and participate in inflammatory reactions and autoimmunity. The interplay of TGF-βand IL-6, expressed at high levels in the bone marrow of myeloma patients, may affect generation of Th17 cells both directly or via other pro-inflammatory cytokines and thereby modulate antitumor immune responses. A detailed analysis of the balance between Tregs and Th17 cells seems necessary in order to design more effective and less toxic modes of immunotherapy myeloma which still is an uncurable malignancy.
机译:多发性骨髓瘤(MM)的发展涉及一系列的遗传改变和骨髓微环境的变化,有利于肿瘤的生长和局部免疫控制的失败。在MM中已经描述了CD4 +和CD8 + T细胞中的数量和功能改变。 T调节细胞(Treg)和T辅助(Th)17细胞之间的平衡代表了维持MM抗肿瘤免疫力的必要先决条件。 Treg在维持自我耐受性和调节针对感染和肿瘤细胞的整体免疫反应中起重要作用。在MM患者中,Treg似乎与骨髓瘤相关的免疫功能障碍有关,因此以它们为靶点可能有助于恢复和增强重要的免疫反应。 Th17细胞可防止真菌和寄生虫感染,并参与炎症反应和自身免疫。在骨髓瘤患者的骨髓中高水平表达的TGF-β和IL-6的相互作用可能直接或通过其他促炎细胞因子影响Th17细胞的生成,从而调节抗肿瘤免疫反应。为了设计更有效和毒性更低的免疫治疗骨髓瘤模式,仍然需要对Tregs和Th17细胞之间的平衡进行详细分析,这仍然是无法治愈的恶性肿瘤。

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