Hematology and Oncology, Department of Internal Medicine 5, University of Erlangen-Nuremberg Erlangen, Germany.
Front Immunol. 2013 Jan 3;3:388. doi: 10.3389/fimmu.2012.00388. eCollection 2012.
There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs(®)) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells.
有广泛的重要药物用于癌症的治疗。除了其已知的对肿瘤细胞的影响外，越来越多的证据表明对免疫系统的调节作用。免疫调节剂（IMiDs(®)）在多发性骨髓瘤或骨髓增生异常综合征患者的治疗中起着重要作用，并且已经表现出抗肿瘤、抗血管生成和免疫刺激作用，特别是对自然杀伤（NK）细胞。酪氨酸激酶抑制剂直接靶向不同的激酶，已知可调节效应 NK 细胞和肿瘤细胞上 NKG2D 配体（NKG2DLs）的表达。去甲基化剂、组蛋白去乙酰化酶和蛋白酶体抑制剂干扰恶性细胞的表观遗传调控和蛋白质降解。有初步迹象表明，这些药物还通过增强 TRAIL 和 NKG2DLs 的表达，使肿瘤细胞对化疗、放疗和 NK 细胞介导的细胞毒性更加敏感。然而，这些药物也可能以剂量和时间依赖的方式损害 NK 细胞的功能。总之，这篇综述提供了关于不同新型分子对免疫系统，特别是 NK 细胞的影响的最新信息。
