title: Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs.
abstract: The effects of high-intensity focused ultrasound (HIFU) on the release of endogenous danger signals from tumor cells and subsequent activation of antigen-presenting cells (APCs) were evaluated in vitro. MC-38 mouse tumor cells were treated using a 1.1 MHz HIFU transducer under two different protocols (P-=6.7 MPa, 30% duty cycle, 5 s vs. P-=10.7 MPa, 3% duty cycle, 30 s) to produce either thermal necrosis or mechanical lysis of the tumor cells. Here, we report that HIFU treatment can cause the release of endogenous danger signals (ATP and hsp60) and exposure of dendritic cells (DCs) and macrophages to the supernatants of HIFU-treated tumor cells leads to an increased expression of co-stimulatory molecules (CD80 and CD86) with enhanced secretion of IL-12 by the DCs and elevated secretion of TNF-alpha by the macrophages. The potency in APC activation produced by mechanical lysis is much stronger than thermal necrosis of the tumor cells. These findings suggest that optimization of treatment strategy may help to enhance HIFU-elicited anti-tumor immunity.
authors.affiliation: Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiao Yi
authors.initials: XY
authors.lastname: Yang
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: H Kim
authors.initials: HK
authors.lastname: Lyerly
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Clay
authors.forename: Pei
authors.initials: P
authors.lastname: Zhong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D013314:Stress, Mechanical; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014465:Ultrasonics; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018834:Chaperonin 60; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000255:Adenosine Triphosphate; D006836:Hydro-Lyases; C045581:lactate dehydratase