人浸润性导管癌相关巨噬细胞中的B7-H4表达
B7-H4 expression in human infiltrating ductal carcinoma‑associated macrophages.
作者信息
Liu Lei, Li Dalin, Chen Shuang, Zhao Ran, Pang Da, Li Dianjun, Fu Zhenkun
机构信息
Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Breast Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
出版信息
Mol Med Rep. 2016 Sep;14(3):2135-42. doi: 10.3892/mmr.2016.5510. Epub 2016 Jul 13.
B7-H4 is a co‑inhibitory molecule of the B7 family, which is expressed on antigen‑presenting cells (APCs) and is able to limit the T‑cell immune response. Macrophages act as professional APCs and are important for immunoregulation of the tumor microenvironment in breast cancer. In order to identify the association between the presence of B7‑H4 on macrophages and infiltrating ductal carcinoma (IDC), the present study investigated the expression of B7‑H4 on macrophages with different polarizations. The expression levels of B7‑H4 in IDC tissues were determined using immunohistochemistry, and the expression of B7‑H4 on macrophages in the breast IDC microenvironment were determined using western blot analysis and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression levels of interleukin (IL)‑6 and IL‑10 were detected in IDC tissues and the supernatants of polarized macrophages using an enzyme‑linked immunosorbent assay and RT‑qPCR. The present study demonstrated that B7‑H4 was overexpressed in IDC tissues and macrophages. In vitro, M1 and M2 macrophages exhibited different expression levels of B7‑H4. IL‑6 and ‑10 exhibited higher expression in the IDC tissues compared with in distal pericarcinomatous tissues. In conclusion, B7‑H4 exhibited overexpression in IDC tissues and cultured macrophage cells. Furthermore, M2 macrophages exhibited higher expression levels of B7‑H4 compared with the M1 subtype. In addition, IL‑6 and ‑10 may be associated with B7‑H4 expression on macrophages of different polarizations in the IDC microenvironment.
B7-H4是B7家族的一种共抑制分子,在抗原呈递细胞(APC)上表达,能够限制T细胞免疫反应。巨噬细胞作为专职APC,对乳腺癌肿瘤微环境的免疫调节很重要。为了确定巨噬细胞上B7-H4的存在与浸润性导管癌(IDC)之间的关联,本研究调查了不同极化状态巨噬细胞上B7-H4的表达。采用免疫组织化学法测定IDC组织中B7-H4的表达水平,采用蛋白质印迹分析和逆转录-定量聚合酶链反应(RT-qPCR)测定乳腺IDC微环境中巨噬细胞上B7-H4的表达。采用酶联免疫吸附测定法和RT-qPCR检测IDC组织和极化巨噬细胞上清液中白细胞介素(IL)-6和IL-10的表达水平。本研究表明,B7-H4在IDC组织和巨噬细胞中过表达。在体外,M1和M2巨噬细胞表现出不同水平的B7-H4表达。与癌旁远端组织相比,IL-6和IL-10在IDC组织中表达更高。总之,B7-H4在IDC组织和培养的巨噬细胞中过表达。此外,与M1亚型相比,M2巨噬细胞表现出更高水平的B7-H4表达。此外,IL-6和IL-10可能与IDC微环境中不同极化状态巨噬细胞上B7-H4的表达有关。