Cheng DA-En, Tsai Ying-Ming, Hsu Ya-Ling, Hou Ming-Feng, Tsai Eing-Mei, Wang Jaw-Yuan, Kan Jung-Yu, Kuo Po-Lin
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Oncol Lett. 2014 Aug;8(2):620-626. doi: 10.3892/ol.2014.2161. Epub 2014 May 19.
Tumor-associated dendritic cells (TADCs) are important in tumor immune surveillance, and it has been reported that the secretion of interleukin (IL)-10 by cancer cells is a major factor involved in the induction of TADCs in the tumor microenvironment. In the present study, IL-10 was found to activate cluster of differentiation (CD)45 protein tyrosine phosphatase (PTPase), inducing a TADC-like phenomenon. The PTPase inhibitor, phenylarsine oxide, and a CD45 inhibitor reversed the IL-10-induced impaired differentiation of the DCs, and also reversed the induction of the TADCs by A549, MDA-MB-231 and SW480 conditioned media, which thus represents a novel therapy to reduce immune surveillance in the tumor microenvironment. The present study is the first to identify that CD45 is involved in IL-10-activated signaling in myeloid lineage cells.
肿瘤相关树突状细胞（TADC）在肿瘤免疫监视中起重要作用，并且有报道称癌细胞分泌白细胞介素（IL）-10是肿瘤微环境中诱导TADC的主要因素。在本研究中，发现IL-10可激活分化簇（CD）45蛋白酪氨酸磷酸酶（PTPase），诱导出类似TADC的现象。PTPase抑制剂氧化苯胂和CD45抑制剂可逆转IL-10诱导的DC分化受损，也可逆转A549、MDA-MB-231和SW480条件培养基对TADC的诱导，因此这代表了一种减少肿瘤微环境中免疫监视的新疗法。本研究首次确定CD45参与髓系细胞中IL-10激活的信号传导。
