The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8+CD45RO-CCR7-CD57+ cells and a lower abundance of CD14+CD33+CD85j+ cells had improved overall survival [median overall survival, range (days) 271, 43-1,247] compared with patients with a lower abundance of CD8+CD45RO-CCR7-CD57+ cells and higher abundance of CD14+CD33+CD85j+ cells (77, 24-1,247 days; P = 0.0442). The results from this prospective-retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

中文翻译：

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在转移性胰腺癌患者的 II 期 GVAX 和 CRS-207 随机研究中，单细胞免疫能力特征与生存相关。


识别患者分层的生物标志物是肿瘤学精准医学工作的基础。在这里，我们确定了与转移性胰腺癌患者的总体生存相关的两个基线循环免疫细胞亚群，这些患者参加了 GVAX 胰腺和 CRS-207 免疫治疗的两项 II 期随机研究。使用单细胞质谱流式细胞仪同时测量从 IIa 期患者亚组 (N = 38) 获得的外周血单核细胞中的 38 种细胞表面或细胞内标记物。 CITRUS 是一种在多维细胞计数数据集中识别分层亚群的算法，用于识别与临床结果相关的单细胞特征。与 CD8+CD45RO-CCR7-CD57+ 细胞丰度较低的患者相比，CD8+CD45RO-CCR7-CD57+ 细胞丰度较低且 CD14+CD33+CD85j+ 细胞丰度较低的患者的总生存期有所改善 [中位总生存期，范围（天） 271, 43-1,247] CD8+CD45RO-CCR7-CD57+ 细胞丰度较高，CD14+CD33+CD85j+ 细胞丰度较高（77, 24-1,247 天；P = 0.0442）。这项前瞻性回顾性生物标志物分析的结果通过流式细胞术在参加 IIb 期研究的 200 名胰腺癌患者中得到验证 (P = 0.0047)。确定的免疫相关性提供了可用于患者分层的潜在预后或预测特征。