Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Prostate and Urological Cancers Program, Yale Comprehensive Cancer Center, New Haven, CT.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Clin Genitourin Cancer. 2018 Apr;16(2):e469-e476. doi: 10.1016/j.clgc.2017.10.010. Epub 2017 Oct 24.
Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown.
Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50 kBq/kg. Concurrent use of prednisone ≤ 10 mg a day was allowed. Peripheral blood samples were collected before and 3 to 4 weeks after the first dose of Ra223 50 kBq/kg. Peripheral blood mononuclear cells were purified and analyzed for the phenotypic and functional characteristics of CD8 T cells using flow cytometry.
One Ra223 treatment did not result in significant change in the overall frequencies of CD8 T cells and their subsets including naive, central memory, and effect memory cells. However, the mean frequency of programmed cell death protein 1-expressing EM CD8 T cells decreased after 1 Ra223 treatment from 20.6% to 14.6% (P = .020), whereas no significant change was observed in the frequencies of CD27-, CD28-, or CTLA4-expressing T cells. One Ra223 treatment was not associated with any significant change in the frequencies of CD8 T cells producing IFN-γ, TNF-α, and IL-13.
One Ra223 treatment is associated with a decreased mean frequency of programmed cell death protein 1-expressing effect memory CD8 T cell without affecting other immune checkpoint molecules or cytokine production. Further investigations are warranted to elucidate the immunologic and clinical significance of our observations and its long-term effects after multiple treatments.
镭 223（Ra223）向前列腺癌成骨转移部位释放高能射线，导致不可修复的双链 DNA 损伤。镭 223 对前列腺癌患者 CD8+T 细胞亚群的影响尚不清楚。
本研究共纳入 15 例有临床指征使用镭 223 治疗且无自身免疫或免疫缺陷的转移性前列腺癌男性患者。患者接受 50 kBq/kg 的镭 223 治疗。允许同时使用≤10mg/天的泼尼松。在接受首剂 50 kBq/kg 镭 223 治疗前和 3 至 4 周后采集外周血样本。分离外周血单个核细胞，采用流式细胞术分析 CD8+T 细胞的表型和功能特征。
单次镭 223 治疗并未导致 CD8+T 细胞及其亚群（包括幼稚、中央记忆和效应记忆细胞）的总体频率发生显著变化。然而，在单次镭 223 治疗后，程序性死亡蛋白 1 表达的 EM CD8+T 细胞的平均频率从 20.6%降至 14.6%（P=0.020），而 CD27-、CD28-或 CTLA4 表达的 T 细胞频率没有明显变化。单次镭 223 治疗与 IFN-γ、TNF-α和 IL-13 产生的 CD8+T 细胞频率无显著变化相关。
单次镭 223 治疗与程序性死亡蛋白 1 表达的效应记忆 CD8+T 细胞的平均频率降低相关，而不影响其他免疫检查点分子或细胞因子的产生。需要进一步研究阐明我们观察结果的免疫学和临床意义及其在多次治疗后的长期影响。
