Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Cancer Treat Rev. 2018 Nov;70:255-264. doi: 10.1016/j.ctrv.2018.10.005. Epub 2018 Oct 10.
Natural Killer cells (NK) are innate effector cells with a critical role in immunosurveillance against different kinds of cancer cells, including Multiple Myeloma (MM). However, the number and/or function of these lymphocytes are strongly reduced during MM progression and in advanced clinical stages. A better understanding of the mechanisms controlling both MM and NK cell biology have greatly contributed to develop novel and combined therapeutic strategies in the treatment of this incurable hematologic malignancy. These include approaches to reverse the immunosuppressive MM microenvironment or potentiate the natural or antibody-dependent cellular cytotoxicity (ADCC) of NK cells. Moreover, chemotherapeutic drugs or specific monoclonal antibodies (mAbs) can render cancer cells more susceptible to NK cell-mediated recognition and lysis; direct enhancement of NK cell function can be obtained by means of immunomodulatory drugs, cytokines and blocking mAbs targeting NK cell inhibitory receptors. Finally, adoptive transfer of ex-vivo expanded and genetically manipulated NK cells is also a promising therapeutic tool for MM. Here, we review current knowledge on complex mechanisms affecting NK cell activity during MM progression. We also discuss recent advances on innovative approaches aimed at boosting the functions of these cytotoxic innate lymphocytes. In particular, we focus our attention on recent preclinical and clinical studies addressing the therapeutic potential of different NK cell-based strategies for the management of MM.
自然杀伤细胞 (NK) 是先天效应细胞，在针对多种癌细胞（包括多发性骨髓瘤 (MM)）的免疫监视中起着关键作用。然而，在 MM 进展和晚期临床阶段，这些淋巴细胞的数量和/或功能会严重降低。更好地了解控制 MM 和 NK 细胞生物学的机制，极大地促进了开发治疗这种不可治愈的血液恶性肿瘤的新的联合治疗策略。这些策略包括逆转抑制性 MM 微环境的方法，或增强 NK 细胞的天然或抗体依赖性细胞毒性 (ADCC)。此外，化疗药物或特定的单克隆抗体 (mAb) 可以使癌细胞更容易被 NK 细胞介导的识别和裂解；通过免疫调节剂、细胞因子和针对 NK 细胞抑制性受体的阻断 mAb 直接增强 NK 细胞功能。最后，体外扩增和基因修饰的 NK 细胞过继转移也是 MM 的一种有前途的治疗工具。在这里，我们综述了影响 MM 进展过程中 NK 细胞活性的复杂机制的最新知识。我们还讨论了旨在增强这些细胞毒性先天淋巴细胞功能的创新方法的最新进展。特别是，我们关注最近的临床前和临床研究，这些研究探讨了不同基于 NK 细胞的策略在 MM 治疗中的潜在应用。
