defective nkt cell activation by cd1d+ tramp prostate tumor cells is corrected by interleukin-12 with alpha-galactosylceramide缺陷nkt细胞激活通过cd1d +流浪汉前列腺肿瘤细胞由与alpha-galactosylceramide interleukin-12纠正.pdf

Defective NKT Cell Activation by CD1d+ TRAMP Prostate Tumor Cells Is Corrected by Interleukin-12 with alpha-Galactosylceramide 1,2 3 1 2 3 Michael Nowak *, Mohammed S. Arredouani , Adrian Tun-Kyi , Ingo Schmidt-Wolf , Martin G. Sanda , Steven P. Balk1, Mark A. Exley1 1 Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Hematology and Oncology, University of Bonn, Bonn, Germany, 3 Division of Urology, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Numerical and functional defects of invariant natural killer T cells (iNKT) have been documented in human and mouse cancers, resulting in a defect in IFN production in several malignancies. iNKT cells recognize glycolipids presented on CD1d molecules by dendritic and related cells, leading to their activation and thereby regulating immune reactions. Activated iNKT cells cytokine secretion and cytotoxicity can inhibit existing and spontaneous tumor growth, progression, and metastasis. We have identified functional iNKT cell defects in the murine TRAMP prostate cancer model. We found that iNKT cells show the ability to migrate into TRAMP prostate tumors. This infiltration was mediated through CCL2: CCR5 chemokine: receptor interaction. Prostate tumor cells expressing CD1d partially activated iNKT cells, as appreciated by up- regulation of CD25, PD-1 and the IL-12R. However, despite inducing up-regulation of these activation markers and, hence, delivering positive signals, prostate t