BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands

• DOI: 10.18632/oncotarget.17834
• Publication Date: 2017-05-12T20:26:59Z
• Authors: Kimberly Mayes; Zeinab Elsayed; Aiman Alhazmi; Michael Waters; Suehyb G. Alkhatib; Mark Roberts; Carolyn Song; Kristen Peterson; Vivian Chan; Nikhil Ailaney; Pumoli Malapati; Tana Blevins; Berislav Lisnić; Catherine I. Dumur; Joseph W. Landry
• Keywords: 0301 basic medicine; 03 medical and health sciences; antitumor immunity; BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.; BPTF ; chromatin remodeling ; antitumor immunity ; NK cell ; heparanase; BPTF; NK cell; BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.; chromatin remodeling; heparanase; Research Paper; 3. Good health

Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in tumor microenvironment (TME). In culture, BPTF direct cytotoxicity receptor (NCR) mediated NK cytolytic to and human lines, demonstrating conserved functions. Blocking NCR1 vivo rescues KD weights, its importance for control of growth. We discovered occupies heparanase (Hpse) regulatory elements, activating expression. Increased results reduced surface abundance NCR co-ligands: heparan sulfate proteoglycans (HSPGs). gain loss function approaches elevated levels suppress cells culture. These suggest activates expression, which turn reduces HSPGs co-ligands, inhibiting activity. Furthermore, gene expression data from tumors shows correlates with immune signatures, supporting roles suppressing immunity. Conditional depletion established enhances immunity, suggesting could provide a novel immunotherapy.