Huang Lefu, Qiao Guoliang, Morse Michael A, Wang Xiaoli, Zhou Xinna, Wu Jiangping, Hobeika Amy, Ren Jun, Lyerly Herbert K
Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing 100038, P.R. China.
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Oncol Lett. 2019 Dec;18(6):5717-5724. doi: 10.3892/ol.2019.10964. Epub 2019 Oct 4.
Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3, CD3CD4, CD3CD8 and CD8CD28) peaked at day 15. Although the percentage of CD4CD25CD127 Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8CD28 T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4CD25CD127 Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of culture. PFS and OS were associated with post/pre-culture CD8CD28 T lymphocyte ratio >2.2 and post/pre-culture CD4CD25CD127 Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.
细胞因子诱导的杀伤细胞（CIK）过继性T细胞免疫疗法已被证明可延长晚期非小细胞肺癌（NSCLC）患者的生存期。本研究的目的是评估在DC-CIK生成过程中发生的效应T细胞扩增和调节性T细胞（Treg）减少是否与接受治疗患者的临床结局改善相关。CIK由163例晚期癌症患者（包括30例NSCLC患者）的外周血单采产物在28天内生成。CIK也由另外65例NSCLC患者在15天内生成。通过查阅患者病历确定接受CIK治疗患者的无进展生存期（PFS）和总生存期（OS）。CIK数量在培养期逐渐增加，在第15天达到峰值，随后略有下降直至第28天。同样，与抗肿瘤活性相关的T细胞亚群（CD3、CD3CD4、CD3CD8和CD8CD28）百分比在第15天达到峰值。虽然CD4CD25CD127 Treg百分比在第7天增加，但随后观察到下降。在95例NSCLC患者中，培养后/培养前CD8CD28 T淋巴细胞比值>2.2的患者与比值≤2.2的患者相比，PFS和OS明显更好。培养后/培养前CD4CD25CD127 Treg比值≤0.6的患者与比值>0.6的患者相比，OS和PFS明显更好。外周血单个核细胞来源的CIK在培养第15天达到峰值扩增。过继性T细胞免疫疗法治疗的晚期NSCLC患者，其PFS和OS与CIK中培养后/培养前CD8CD28 T淋巴细胞比值>2.2以及培养后/培养前CD4CD25CD127 Treg比值<0.6相关。目前正在进一步努力优化DC-CIK输注用于癌症免疫治疗。
