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随机对照 III 期试验:肺癌患者区域淋巴结来源的激活细胞毒性 T 细胞和树突状细胞辅助化疗免疫治疗。

Randomized controlled phase III trial of adjuvant chemoimmunotherapy with activated cytotoxic T cells and dendritic cells from regional lymph nodes of patients with lung cancer.

机构信息

Department of Thoracic Surgery, Saiseikai-Narashino Hospital, Izumi-cho 1-1-1, Narashino, Chiba, 275-8580, Japan.

Department of Thoracic Surgery, Chiba Cancer Center, Chiba, Japan.

出版信息

Cancer Immunol Immunother. 2018 Aug;67(8):1231-1238. doi: 10.1007/s00262-018-2180-6. Epub 2018 May 31.

Abstract

Randomized controlled trial of adjuvant chemoimmunotherapy for lung cancer indicated a significant advantage in patients receiving immunotherapy. Herein we report the final results and immunological analysis with a median follow-up of 59.6 months. Patients with post-surgical lung cancer were randomly designated to receive either chemoimmunotherapy (group A, immunotherapy arm) or chemotherapy (group B, control arm). The immunotherapy comprised the adoptive transfer of autologous activated killer T cells and dendritic cells (AKT-DC). The 2- and 5-year overall survival (OS) rates were 96.0 and 69.4% in group A and 64.7 and 45.1% in group B, respectively. Multivariate analysis results revealed that the hazard ratio was 0.439. The 2- and 5-year recurrence-free survival rates were 70.0 and 57.9% in group A and 43.1 and 31.4% in group B, respectively. Subgroup analysis for the OS between treatment groups indicated that younger patients (≤ 55 years: HR 0.098), males (HR 0.474), patients with adenocarcinoma (HR 0.479), patients with stage III cancer (HR 0.399), and those who did not receive preoperative chemotherapy (HR 0.483) had lower HRs than those in the other groups. Immunological analysis of cell surface markers in regional lymph nodes of subjects receiving immunotherapy indicated that the CD8/CD4 T-cell ratio was elevated in survivors. Patients with non-small-cell lung cancer benefited from adoptive cellular immunotherapy as an adjuvant to surgery. Patients with stage III cancer, those with adenocarcinoma, and those not receiving preoperative chemotherapy were good candidates. Lastly, cytotoxic T cells were important for a favorable chemoimmunotherapy outcome.

摘要

一项针对肺癌辅助化免疫治疗的随机对照临床试验表明,免疫治疗组患者具有显著优势。在此,我们报告中位随访 59.6 个月的最终结果和免疫分析。手术后肺癌患者被随机分为接受化免疫治疗(A 组,免疫治疗组)或化疗(B 组,对照组)。免疫治疗包括自体激活杀伤 T 细胞和树突状细胞(AKT-DC)的过继转移。A 组的 2 年和 5 年总生存率(OS)分别为 96.0%和 69.4%,B 组分别为 64.7%和 45.1%。多变量分析结果显示,风险比为 0.439。A 组的 2 年和 5 年无复发生存率分别为 70.0%和 57.9%,B 组分别为 43.1%和 31.4%。治疗组 OS 的亚组分析表明,≤55 岁的患者(HR 0.098)、男性(HR 0.474)、腺癌患者(HR 0.479)、III 期癌症患者(HR 0.399)和未接受术前化疗的患者(HR 0.483)的 HR 低于其他组。接受免疫治疗的受试者区域淋巴结细胞表面标志物的免疫分析表明,存活者的 CD8/CD4 T 细胞比值升高。非小细胞肺癌患者受益于手术辅助的细胞免疫治疗。III 期癌症患者、腺癌患者和未接受术前化疗的患者是良好的候选者。最后,细胞毒性 T 细胞对化免疫治疗的良好效果很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c37/11028147/332d9686e8bd/262_2018_2180_Fig1_HTML.jpg

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