Seta Clinic Group, Tokyo, Japan; Department of Next-Generation Cell and Immune Therapy, Juntendo University School of Medicine, Tokyo, Japan.
Kanazawa Advanced Medical Center, Kanazawa, Japan.
Cytotherapy. 2020 Jun;22(6):329-336. doi: 10.1016/j.jcyt.2020.02.008. Epub 2020 Apr 14.
Activated γδT cells have been shown to exhibit cytotoxicity against tumor cells. However, the efficacy of γδT cell immunotherapy for a large number of patients with solid tumors remains unclear. In this study, we examined the efficacy of γδT cell immunotherapy using in vitro-activated γδT lymphocytes in combination with standard therapies in terms of the survival of patients with solid tumors, and determined prognostic factor for γδT cell immunotherapy.
131 patients enrolled in this study received γδT cell immunotherapy with or without standard therapies. Their overall survival was analyzed by the Kaplan-Meier with log-rank test and Cox regression methods. Immunological analysis was performed by flow cytometry (FCM) before and after six cycles of γδT cell immunotherapy.
Multivariable analysis revealed that patients who showed stable disease (SD) and partial response (PR) to γδT cell immunotherapy showed better prognosis than those with a progressive disease (PD) (P = 0.0269, hazard ratio [HR], 0.410, 95% confidence interval [CI], 0.190-0.901). Furthermore, when immunological parameters were examined by FCM, the high Vγ9/γδT ratio (i.e., the high purity of the Vγ9 cells within the adoptively transferred γδT cells) before treatment was found to be a good prognostic factor for γδT cell immunotherapy (P = 0.0142, HR, 0.328, 95% CI, 0.125-0.801). No serious adverse events were reported during γδT cell immunotherapy.
Thus, γδT cell immunotherapy might extend the survival of patients with solid tumors.
已证实活化的γδT 细胞对肿瘤细胞具有细胞毒性。然而，γδT 细胞免疫疗法在大量实体瘤患者中的疗效尚不清楚。在这项研究中，我们研究了使用体外活化的γδT 淋巴细胞联合标准疗法进行γδT 细胞免疫疗法对实体瘤患者生存的影响，并确定了γδT 细胞免疫疗法的预后因素。
本研究纳入了 131 例接受γδT 细胞免疫治疗联合或不联合标准治疗的患者。采用 Kaplan-Meier 对数秩检验和 Cox 回归方法分析患者的总生存期。在接受 6 个周期的γδT 细胞免疫治疗前后，采用流式细胞术（FCM）进行免疫分析。
多变量分析显示，γδT 细胞免疫治疗后疾病稳定（SD）和部分缓解（PR）的患者预后优于疾病进展（PD）的患者（P=0.0269，风险比 [HR]，0.410，95%置信区间 [CI]，0.190-0.901）。此外，通过 FCM 检查免疫参数时，发现治疗前高 Vγ9/γδT 比值（即，过继转移的γδT 细胞中 Vγ9 细胞的高纯度）是γδT 细胞免疫治疗的良好预后因素（P=0.0142，HR，0.328，95%CI，0.125-0.801）。在γδT 细胞免疫治疗过程中未报告严重不良事件。
因此，γδT 细胞免疫疗法可能延长实体瘤患者的生存时间。
