Markowitz Joseph, Brooks Taylor R, Duggan Megan C, Paul Bonnie K, Pan Xueliang, Wei Lai, Abrams Zachary, Luedke Eric, Lesinski Gregory B, Mundy-Bosse Bethany, Bekaii-Saab Tanios, Carson William E
Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.
Cancer Immunol Immunother. 2015 Feb;64(2):149-59. doi: 10.1007/s00262-014-1618-8. Epub 2014 Oct 11.
Elevated levels of myeloid-derived suppressor cells (MDSCs) induced by tumor-derived factors are associated with inhibition of immune responses in patients with gastrointestinal malignancies. We hypothesized that pro-MDSC cytokines and levels of MDSC in the peripheral blood would be elevated in pancreatic adenocarcinoma patients with progressive disease. Peripheral blood mononuclear cells (PBMCs) were isolated from 16 pancreatic cancer patients undergoing chemotherapy and phenotyped for MDSC using a five antigen panel (CD33, HLA-DR, CD11b, CD14, CD15). Patients with stable disease had significantly lower MDSC levels in the peripheral blood than those with progressive disease (1.41 ± 1.12 vs. 5.14 ± 4.58 %, p = 0.013, Wilcoxon test). A cutoff of 2.5 % MDSC identified patients with progressive disease. Patients with ECOG performance status ≥2 had a weaker association with increased levels of MDSC. Plasma was obtained from 15 chemonaive patients, 13 patients undergoing chemotherapy and 9 normal donors. Increases in the levels of pro-MDSC cytokines were observed for pancreatic cancer patients versus controls, and the pro-MDSC cytokine IL-6 was increased in those patients undergoing chemotherapy. This study suggests that MDSC in peripheral blood may be a predictive biomarker of chemotherapy failure in pancreatic cancer patients.
肿瘤衍生因子诱导的髓源性抑制细胞（MDSC）水平升高与胃肠道恶性肿瘤患者的免疫反应抑制有关。我们假设，疾病进展的胰腺腺癌患者外周血中促MDSC细胞因子和MDSC水平会升高。从16例接受化疗的胰腺癌患者中分离外周血单个核细胞（PBMC），并使用五抗原面板（CD33、HLA-DR、CD11b、CD14、CD15）对MDSC进行表型分析。疾病稳定的患者外周血中的MDSC水平显著低于疾病进展的患者（1.41±1.12%对5.14±4.58%，p = 0.013，Wilcoxon检验）。MDSC水平为2.5%作为临界值可识别疾病进展的患者。东部肿瘤协作组（ECOG）体能状态≥2的患者与MDSC水平升高的关联较弱。从15例初治患者、13例正在接受化疗的患者和9名正常供体中获取血浆。与对照组相比，胰腺癌患者促MDSC细胞因子水平升高，且正在接受化疗的患者促MDSC细胞因子白细胞介素-6升高。这项研究表明，外周血中的MDSC可能是胰腺癌患者化疗失败的预测生物标志物。
