Tjomsland Vegard, Niklasson Lina, Sandström Per, Borch Kurt, Druid Henrik, Bratthäll Charlotte, Messmer Davorka, Larsson Marie, Spångeus Anna
Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Clin Dev Immunol. 2011;2011:212810. doi: 10.1155/2011/212810. Epub 2011 Dec 6.
Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGFβ, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.
肿瘤微环境由肿瘤细胞、成纤维细胞和浸润性免疫细胞组成,它们共同作用,营造出有利于肿瘤进展的炎症环境。本研究旨在探讨促纤维增生性基质在胰腺导管腺癌(PDAC)中对炎症因子表达、免疫细胞浸润及其对临床结局影响的作用。与对照组相比,所检测的PDAC组织中免疫调节和趋化因子(IL-6、TGFβ、IDO、COX-2、CCL2和CCL20)以及与巨噬细胞、髓样和浆细胞样树突状细胞(DCs)相对应的免疫细胞特异性标志物的表达水平显著升高。此外,短期存活者的DC标志物水平最低。免疫染色表明,不同的免疫细胞和炎症因子主要定位于促纤维增生性基质中。调节炎症性肿瘤微环境以促进DCs的募集和单核细胞分化为功能性DCs的疗法可能会改善PDAC患者的生存率。