PDF(Pubmed)
Abstract：
UNASSIGNED: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.
UNASSIGNED: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.
UNASSIGNED: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.
UNASSIGNED: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
UNASSIGNED: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.
UNASSIGNED: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.
UNASSIGNED: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.
摘要：
■许多癌症转移到胸膜，导致引起呼吸困难和不适的积液。不管是什么组织的起源,胸膜恶性肿瘤是侵袭性的，并且是致命的，没有延长寿命的治疗方法。胸膜间皮单层通过紧密连接连接，形成包含的生物反应器状空间，浓缩由间皮分泌的细胞因子和趋化因子，肿瘤，和浸润免疫细胞。这个空间代表了一个深刻地影响肿瘤和免疫细胞行为的独特环境。定义胸膜分泌体是合理开发局部胸膜内免疫治疗的重要步骤。
■我们使用40分析物面板和Luminex多路复用技术，在多种癌症中测量了252个恶性胸腔积液（MPE）样品的细胞因子/趋化因子含量。
■十一种分析物始终以≥10.0pM的浓度存在：CXCL10/IP10（几何平均值=672.3pM），CCL2/MCP1(562.9pM),sIL-6Rα（403.1pM），IL-6（137.6pM），CXCL1/GRO(80.3pM),TGFβ1（76.8pM），CCL22/MDC(54.8pM),CXCL8/IL-8（29.2pM），CCL11/Eotaxin（12.6pM），IL-10（11.3pM），和G-CSF(11.0pM)。都能够介导趋化性，促进上皮向间充质转化，或者免疫抑制,据报道,许多是由细胞因子IL-6及其可溶性受体介导的促炎细胞因子级联的下游。
■数据表明，在转移到胸膜的上皮癌中，几种细胞因子和趋化因子的浓度很高，并支持了以下观点：胸膜环境是导致MPE临床过程的主要因素。sIL-6Rα与IL-6摩尔比为2.7，确保几乎所有上皮，胸膜环境中的免疫和血管内皮细胞受到IL-6信号的影响。IL-6在MPE的发病机理中可能发挥的核心作用支持靶向IL-6/IL-6R轴的治疗方法。
■我们使用40分析物面板和Luminex多路复用技术，在多种癌症中测量了252个恶性胸腔积液（MPE）样品的细胞因子/趋化因子含量。
■十一种分析物始终以≥10.0pM的浓度存在：CXCL10/IP10（几何平均值=672.3pM），CCL2/MCP1(562.9pM),sIL-6Rα（403.1pM），IL-6（137.6pM），CXCL1/GRO(80.3pM),TGFβ1（76.8pM），CCL22/MDC(54.8pM),CXCL8/IL-8（29.2pM），CCL11/Eotaxin（12.6pM），IL-10（11.3pM），和G-CSF(11.0pM)。都能够介导趋化性，促进上皮向间充质转化，或者免疫抑制,据报道,许多是由细胞因子IL-6及其可溶性受体介导的促炎细胞因子级联的下游。
■数据表明，在转移到胸膜的上皮癌中，几种细胞因子和趋化因子的浓度很高，并支持了以下观点：胸膜环境是导致MPE临床过程的主要因素。sIL-6Rα与IL-6摩尔比为2.7，确保几乎所有上皮，胸膜环境中的免疫和血管内皮细胞受到IL-6信号的影响。IL-6在MPE的发病机理中可能发挥的核心作用支持靶向IL-6/IL-6R轴的治疗方法。
