Mucin1 and poly I:C activates dendritic cells and effectively eradicates pituitary tumors as a prophylactic vaccine

作者:Sui, Dehua; Ma, Lixin; Li, Meng; Shao, Wei; Du, Hongpeng; Li, Ke; Li, Zhenzhu; Li, Zefu*
来源:Molecular Medicine Reports, 2016, 13(4): 3675-3683.
DOI:10.3892/mmr.2016.4964

摘要

Pituitary tumors are the most common type of cancer within the central nervous system. In the present study, the expression levels of mucin 1 (Muc1) were examined in invasive and non-invasive pituitary tumor samples, and the results of immunohistochemical staining and Western blot analysis demonstrated marked positive expression of Muc1. In addition, Muc1 + polyinosinic: polycytidylic acid (poly I:C) was found to stimulate the expression levels of the surface molecules cluster of differentiation (CD) 40, CD83 and CD80, and HLA-DRm and decreased the expression of CD14 in the dendritic cells, determined using fluorescence-activated cell sorting. The secretions of interleukin (IL)-6, tumor necrosis factor-a and IL-1 beta cytokines were also significantly induced, in a dose-dependent manner. In in vivo experiments, a higher percentage of CD3(+)CD4(+) T lymphocytes was detected, and the levels of interferon-gamma and IL-2 in the splenocytes were also upregulated. Furthermore, the combination treatment of Muc1 with poly I: C increased anti-Muc1 IgM and anti-Muc1 IgG titers, and altered the balance of IgG2a and IgG1, all of which increased the T helper (Th)1 polarized immune response. Thus, the tumor antigen, Muc1, with poly I: C may produce potent protective effects, which polarize immune responses towards Th1, and elicit antitumor immunity to inhibit the progression of pituitary tumors.