Zhou Yun, Chen Chang-Long, Jiang Sen-Wei, Feng Yanling, Yuan Linjing, Chen Ping, Zhang Lan, Huang Shuting, Li Jundong, Xia Jian-Chuan, Zheng Min
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
Department of Gynecology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
Oncoimmunology. 2018 Nov 11;8(2):e1528411. doi: 10.1080/2162402X.2018.1528411. eCollection 2019.
Cytokine-induced killer (CIK) cells are demonstrated to possess potent cytolytic effect against ovarian cancer cells and . However, the clinical efficacy of maintenance therapy of CIK cells in patients with epithelial ovarian cancer (EOC) after first-line treatment remains unclear. This retrospective study included 646 cases of postoperative EOC patients, 72 of which received chemotherapy and sequential immunotherapy (CIT group), and 574 of which received only chemotherapy (Control group). Patients in the CIT group received at least four cycles of CIK cell (range 8.0 × 10 - 1.3 × 10 cells) transfusion, with the interval of each cycle being 2 weeks. Survival analysis showed a significantly higher overall survival (OS) rate in the CIT group compared with the control group, as well as a favorable progression-free survival (PFS). Univariate and multivariate analyses indicated that adjuvant CIT was an independent prognostic factor for the OS of patients with EOC. Furthermore, subgroup analyses showed that adjuvant CIT significantly improved the OS of patients older than 45 years, with CA125 ≤ 1000, or with moderate or poorly differentiated tumors, and prolonged the PFS of patients with residual disease > 1 cm. Additionally, Kaplan-Meier analyses revealed that a higher fraction of CD3CD8/CD3CD56 phenotypes or lower percentage of CD3CD4/CD3CD56 phenotypes in the infused CIK cells significantly associated with better survival of patients with EOC. Furthermore, across all processes of CIK cell immunotherapy in the CIT group, 12.5% (9/72) of patients developed self-limiting light fevers and shivering at grade 1 or 2. No immunotherapy-related serious reactions were recorded. These data indicate that adjuvant CIT with CIK cells is an effective therapeutic approach to prolonging the survival of EOC patients.
细胞因子诱导的杀伤(CIK)细胞已被证明对卵巢癌细胞具有强大的细胞溶解作用。然而,CIK细胞维持治疗在上皮性卵巢癌(EOC)患者一线治疗后的临床疗效仍不清楚。这项回顾性研究纳入了646例EOC术后患者,其中72例接受了化疗及序贯免疫治疗(CIT组),574例仅接受了化疗(对照组)。CIT组患者接受了至少四个周期的CIK细胞(范围为8.0×10 - 1.3×10个细胞)输注,每个周期的间隔为2周。生存分析显示,CIT组的总生存(OS)率显著高于对照组,无进展生存期(PFS)也较好。单因素和多因素分析表明,辅助性CIT是EOC患者OS的独立预后因素。此外,亚组分析显示,辅助性CIT显著改善了年龄大于45岁、CA125≤1000或肿瘤为中分化或低分化患者的OS,并延长了残留病灶>1 cm患者的PFS。此外,Kaplan-Meier分析显示,输注的CIK细胞中CD3CD8/CD3CD56表型比例较高或CD3CD4/CD3CD56表型比例较低与EOC患者更好的生存显著相关。此外,在CIT组CIK细胞免疫治疗的所有过程中,12.5%(9/72)的患者出现了1级或2级自限性轻度发热和寒战。未记录到与免疫治疗相关的严重反应。这些数据表明,CIK细胞辅助性CIT是延长EOC患者生存的有效治疗方法。