Chen Jingyi, Chen Yusong, Feng Fenglan, Chen Cheng, Zeng Haikang, Wen Shuai, Xu Xin, He Jianxing, Li Jin
State Key Laboratory of Respiratory Disease, the Thoracic Surgery Department, the First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
J Thorac Dis. 2018 Dec;10(12):6711-6721. doi: 10.21037/jtd.2018.10.111.
Cytokine-induced killer (CIK) cells and natural killer (NK) cells are employed by two different approaches to adoptive cell immunotherapy for cancer. It has been reported that adoptive cell immunotherapy could prolong the overall survival (OS) of advanced cancer patients. The introduction of agents that induce immune checkpoint blockades has improved the efficacy of immune-mediated therapy for metastatic cancers. However, the effects of combining a checkpoint inhibitor with CIK cells or NK cells to target non-small cell lung cancer (NSCLC)remain unknown.
The present study investigated the effects of combining CIK cells with a programmed cell death protein-1 (PD-1) inhibitor (an anti-PD-1 monoclonal antibody). During the expansion cultivation, the addition of the PD-1 antibody promoted CIK-mediated cytotoxicity in H1975 lung adenocarcinoma cells. Co-cultivation of CIK cells with the PD-1 antibody for 6 days induced CD3CD56 T cell expansion, with increases in the levels of CD107a and interferon γ (IFN-γ).
When NK cells were co-cultured with 5 µg/mL of an anti-programmed death-ligand 1 (PD-L1) mAb for 24 hours at an effector cell: target ratio of 10:1, it led to more potent cytotoxicity compared to other time points and concentrations. However, combining NK cells with the anti-PD-L1 mAb showed no significant advantages over treatment with NK cells alone.
Our results suggest that combining CIK cells with PD-1 blockade before transfusion might improve the efficiency of CIK therapy for NSCLC patients. This effect does not seem to occur for NK cell therapy.
细胞因子诱导的杀伤细胞（CIK）和自然杀伤细胞（NK）通过两种不同的方法用于癌症的过继性细胞免疫治疗。据报道，过继性细胞免疫治疗可延长晚期癌症患者的总生存期（OS）。免疫检查点阻断剂的引入提高了转移性癌症免疫介导治疗的疗效。然而，将检查点抑制剂与CIK细胞或NK细胞联合用于治疗非小细胞肺癌（NSCLC）的效果尚不清楚。
本研究调查了将CIK细胞与程序性细胞死亡蛋白1（PD-1）抑制剂（抗PD-1单克隆抗体）联合使用的效果。在扩增培养过程中，添加PD-1抗体可增强CIK对H1975肺腺癌细胞的细胞毒性。CIK细胞与PD-1抗体共培养6天可诱导CD3CD56 T细胞扩增，同时CD107a和干扰素γ（IFN-γ）水平升高。
当NK细胞与5μg/mL抗程序性死亡配体1（PD-L1）单克隆抗体以效应细胞：靶细胞比例为10:1共培养24小时时，与其他时间点和浓度相比，其细胞毒性更强。然而，将NK细胞与抗PD-L1单克隆抗体联合使用与单独使用NK细胞治疗相比，没有显著优势。
我们的结果表明，在输注前将CIK细胞与PD-1阻断联合使用可能会提高CIK疗法对NSCLC患者的疗效。这种效果在NK细胞治疗中似乎不会出现。
