Sharma Vinit, Sachdeva Naresh, Gupta Vikas, Nada Ritambhra, Jacob Justin, Sahni Daisy, Aggarwal Anjali
Department of Anatomy, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Scand J Immunol. 2021 Dec;94(6):e13107. doi: 10.1111/sji.13107. Epub 2021 Oct 15.
Chronic inflammation favours the expansion of myeloid-derived suppressor cells (MDSCs) by secreting pro-inflammatory mediators. The role of MDSCs in mediating immunosuppression in pancreatic adenocarcinoma and in defining a premalignant route from chronic pancreatitis remains unclear. We aimed to study the immunosuppressive potential of all subsets of MDSCs and their correlation with inflammatory cytokines in pancreatic adenocarcinoma and chronic pancreatitis. Relative frequencies of MDSCs, immunosuppressive markers arginase-1 (ARG-1), programmed death-ligand 1 (PD-L1), reactive oxygen species (ROS) and cytokines in circulation and surgically resected local pancreatic tissue of chronic pancreatitis and pancreatic adenocarcinoma patients were analysed by multicolour flow cytometry and cytokine bead array, respectively. Levels of cytokines involved in MDSCs activation were analysed by ELISA, and the immunosuppressive nature of MDSCs was confirmed by T-cell suppression assay. Frequencies of circulating MDSCs and ARG-1, PD-L1, and ROS were significantly higher in pancreatic adenocarcinoma than healthy controls and showed a significant positive correlation with MDSCs burden in cancer tissue. Serum levels of cytokines IL-6, IL-8 and IL-10 were significantly elevated in pancreatic adenocarcinoma. IL-6 serum levels showed a significant positive correlation with frequencies of circulating MDSCs in pancreatic adenocarcinoma patients, and MDSCs mediated suppression of T-cell proliferation in vitro was associated with elevated IL-6 levels in the cell culture medium. Collectively, our results suggest that IL-6 plays a crucial role in the expansion of MDSCs and activating their immunosuppressive nature in pancreatic adenocarcinoma. The relative frequency of MDSCs in circulation can be used as a potential diagnostic biomarker for pancreatic cancer.
慢性炎症通过分泌促炎介质促进髓源性抑制细胞（MDSCs）的扩增。MDSCs在介导胰腺腺癌免疫抑制以及确定从慢性胰腺炎到癌前病变途径中的作用仍不清楚。我们旨在研究MDSCs所有亚群的免疫抑制潜能及其与胰腺腺癌和慢性胰腺炎中炎性细胞因子的相关性。分别通过多色流式细胞术和细胞因子珠阵列分析慢性胰腺炎和胰腺腺癌患者循环血及手术切除的局部胰腺组织中MDSCs的相对频率、免疫抑制标志物精氨酸酶-1（ARG-1）、程序性死亡配体1（PD-L1）、活性氧（ROS）和细胞因子。通过酶联免疫吸附测定（ELISA）分析参与MDSCs激活的细胞因子水平，并通过T细胞抑制试验证实MDSCs的免疫抑制特性。胰腺腺癌患者循环血中MDSCs以及ARG-1、PD-L1和ROS的频率显著高于健康对照，且与癌组织中MDSCs负荷呈显著正相关。胰腺腺癌患者血清中细胞因子IL-6、IL-8和IL-10水平显著升高。胰腺腺癌患者血清IL-6水平与循环血中MDSCs频率呈显著正相关，且体外MDSCs介导的T细胞增殖抑制与细胞培养基中IL-6水平升高有关。总体而言，我们的结果表明IL-6在胰腺腺癌中MDSCs的扩增及其免疫抑制特性激活中起关键作用。循环血中MDSCs的相对频率可作为胰腺癌潜在的诊断生物标志物。
