自然杀伤细胞相关的肺癌微环境及免疫治疗

Natural Killer Cell-associated Lung Cancer Microenvironment and Immunotherapy

自然杀伤细胞(NK细胞)是针对病毒感染细胞和癌细胞的细胞毒性淋巴细胞,可以通过不同方式杀死癌细胞。在肺癌中,免疫抑制性肿瘤微环境限制了NK细胞的活化;此外,氧气及营养物质的缺乏、肿瘤衍生代谢产物以及肥胖症等也会影响NK细胞的活化,从而抑制NK细胞的抑瘤作用。在高度免疫抑制肿瘤微环境中,NK细胞可通过释放细胞外囊泡、介导Fc受体表达等方式发挥抗肿瘤作用。由于手术、放化疗、靶向治疗等肺癌治疗方法的限制,需要寻求新的治疗手段,以确保肺癌的有效治疗。目前,在肺癌等实体瘤的治疗中,基于NK细胞的免疫治疗取得了令人满意的结果,包括离体扩增NK细胞过继转移疗法、针对Dickkopf相关蛋白2抗体的NK细胞的细胞激活疗法以及嵌合抗原受体转导的NK细胞疗法等。

Natural killer cell(NK cell)are cytotoxic lymphocytes against virus-infected cells and cancer cells,which can kill cancer cells in different ways.In lung cancer,immunosuppressive tumor microenvironment limits the activation of NK cell;in addition,the lack of oxygen and nutrients,tumor-derived metabolites and obesity also affect the activation of NK cell,thus inhibiting the anti-tumor effect of NK cell.In highly immunosuppressed tumor microenvironment,NK cell can play an anti-tumor role by releasing extracellular vesicles and mediating the expression of Fc receptors.Due to the limitations of surgery,chemoradiotherapy,targeted therapy and other lung cancer treatment methods,we need to seek new treatment methods to ensure the effective treatment of lung cancer.At present,in the treatment of solid tumors such as lung cancer,immunotherapy based on NK cell has achieved satisfactory results,including adoptive transfer therapy of ex vivo expansion of NK cell,NK cell activation therapy against Dickkopf related protein 2 antibody,and chimeric antigen receptor transduction NK cell therapy etc.