Gonzalez-Rodriguez Ana P, Villa-Álvarez Mónica, Sordo-Bahamonde Christian, Lorenzo-Herrero Seila, Gonzalez Segundo
Department of Hematology, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain.
Instituto Universitario de Oncología del Principado de Asturias, IUOPA, 33006 Oviedo, Spain.
J Clin Med. 2019 Sep 27;8(10):1557. doi: 10.3390/jcm8101557.
Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases.
自然杀伤（NK）细胞具有杀伤癌细胞的先天能力，然而，肿瘤细胞可能获得逃避免疫反应的能力，从而导致恶性肿瘤。恢复或增强NK细胞的这种天然抗肿瘤活性已成为癌症尤其是血液系统癌症的一种相关治疗方法。使用通过连接NK细胞上的CD16受体来促进抗体依赖性细胞介导的细胞毒性（ADCC）的肿瘤特异性抗体已成为许多血液系统恶性肿瘤的标准治疗方法。造血干细胞移植是另一种利用NK细胞对癌细胞的同种异体反应性的关键治疗策略。该策略可通过过继转移NK细胞来优化，这些NK细胞可能预先经过扩增、激活或重定向（嵌合抗原受体（CAR）-NK细胞）以对抗癌细胞。NK细胞的抗肿瘤活性也可通过细胞因子或免疫刺激药物如来那度胺或泊马度胺来增强。最后，针对血液系统癌症所形成的免疫颠覆机制，特别是使用阻断NK细胞抑制性受体和检查点蛋白的抗体，是这些恶性疾病中颇具前景的新型治疗方法。
