Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them.
Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them.
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DOI：
10.3390/ijms22031103
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发表时间：
2021-01-22
影响因子：
5.6
通讯作者：
Fionda C
中科院分区：
文献类型：
--
作者：
Cippitelli M;Stabile H;Kosta A;Petillo S;Gismondi A;Santoni A;Fionda C
Ikaros zing-finger 家族转录因子 (IKZF TF) 是淋巴细胞发育和分化的重要调节因子，在 B 细胞恶性肿瘤中也高度表达，包括多发性骨髓瘤 (MM)，它们是癌细胞生长和存活所必需的。此外，IKZF 转录因子对许多免疫细胞的功能特性具有负面控制。因此，这些蛋白质的靶向对癌症具有相关的治疗意义。事实上，越来越多的证据表明，Ikaros 和 Aiolos（IKZF 家族的两个成员）在恶性浆细胞以及适应性和先天淋巴细胞中的下调是免疫调节药物 (IMiD) 抗骨髓瘤活性的关键。本综述重点关注 MM 中 IKZF TF 相关通路。特别是，我们将探讨 IKZF TF 的消耗如何通过降低 MM 细胞的存活和增殖来对 MM 细胞产生细胞毒性作用，并同时增强抗肿瘤免疫反应，从而有助于 IMiD 的治疗效果，IMiD 是治疗这种肿瘤的基石。
The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.
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