title: Specific antitumour immunity of HIFU-activated cytotoxic T lymphocytes after adoptive transfusion in tumour-bearing mice.
abstract: OBJECTIVE
  The aim of this study was to investigate the specific anti-tumour immunity of cytotoxic T lymphocytes (CTL) activated by high-intensity focused ultrasound (HIFU) after adoptive transfer in a murine tumour model.
  
  
  METHODS
  H22 tumour-bearing mice were treated by either HIFU or sham-HIFU, while naïve syngeneic mice were used as controls. They were sacrificed and the spleens were harvested 14 days after HIFU. T lymphocytes were obtained from the spleens, and then adoptively transferred into 40 mice each bearing a 3-day implanted H22 tumour. On day 14 after adoptive transfer, 10 mice were sacrificed in each group for assessment of the number of tumour-infiltrating T lymphocytes and interferon-gamma (IFN-γ) secreting cells. The remaining 30 mice were continuously observed for 60 days, and tumour growth, progression and survival were recorded.
  
  
  RESULTS
  HIFU significantly increased peripheral blood CD3(+), CD4(+) levels and CD4(+)/CD8(+) ratio (P < 0.05), CTL cytotoxicity (P < 0.01) and IFN-γ and TNF-α secretion (P < 0.01) in H22 tumour-bearing mice. Adoptive transfer of HIFU-activated T lymphocytes into the autologous tumour-bearing mice induced a significant increase of tumour-infiltrating T lymphocytes and IFN-γ-secreting cells (P < 0.001). Compared to the control and sham-HIFU groups, HIFU-activated lymphocytes elicited significant inhibition of in vivo tumour growth (P < 0.01) and progression (P < 0.0001), and longer survival time in the tumour-bearing mice (P < 0.001).
  
  
  CONCLUSIONS
  HIFU could enhance CTL's specific antitumour immunity. Adoptive transfer of HIFU-activated T lymphocytes could increase local antitumour immunity, and elicit stronger inhibition on tumour growth and progression, with more survival benefit in the autologous tumour-bearing mice.
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Ran
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.
authors.forename: Xun-Peng
authors.initials: XP
authors.lastname: Xie
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.
authors.forename: Ji-Zhu
authors.initials: JZ
authors.lastname: Xia
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Xie
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Fan
authors.affiliation: a Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University , Chongqing , China and.|b Nuffield Department of Surgical Sciences, University of Oxford , Oxford , UK.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D057086:High-Intensity Focused Ultrasound Ablation; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
keywords: Cytotoxic T lymphocyte; high-intensity focused ultrasound; immunotherapy; thermal ablation; tumour