Division of Paediatric Oncology, Department of Paediatrics, National University Hospital Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 12, Singapore, 119228, Singapore.
Curr Oncol Rep. 2019 Sep 10;21(10):93. doi: 10.1007/s11912-019-0837-8.
We aim to review the most recent findings in the use of NK cells in childhood cancers.
Natural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. Cytotoxicity to solid tumors (rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma) is seen with graft versus tumor effect in transplant and in combination with antibodies. Challenges lie in the microenvironment which is suppressive for NK cells. NK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges.
本文旨在综述自然杀伤（NK）细胞在儿童癌症中的最新应用研究进展。
NK 细胞对肿瘤细胞具有细胞毒性。在儿科白血病中，NK 细胞过继转移可使未缓解的患儿桥接至移植。白细胞介素（IL-2、IL-15）可增强 NK 细胞的功能。NK 细胞嵌合抗原受体（CAR）疗法具有以下优势：半衰期较短，从而减少慢性毒性；当使用异体细胞时，移植物抗宿主病的风险较低；NK 细胞能够识别下调 MHC 以逃避 T 细胞识别的肿瘤细胞；细胞因子风暴的可能性较小。在移植和与抗体联合应用中，NK 细胞可发挥移植物抗肿瘤作用，杀伤横纹肌肉瘤、尤文肉瘤和神经母细胞瘤等实体瘤。但 NK 细胞在肿瘤微环境中会受到抑制，这是一个挑战。NK 细胞免疫疗法在儿童癌症中的应用具有广阔前景，目前的研究工作旨在克服这些挑战。
