title: Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity.
abstract: OBJECTIVE
  To evaluate the influence of subtotal radiofrequency (RF) ablation on a tumor-specific immune response in a murine tumor model and to explore the role of intratumoral dendritic cells (ITDCs) in mediating this effect.
  
  
  METHODS
  Animal work was performed according to an approved protocol and in compliance with the National Cancer Institute Animal Care and Use Committee guidelines and regulations. A murine urothelial carcinoma (MB49) model expressing the male minor histocompatibility (HY) antigen was inoculated subcutaneously in female mice. Fourteen days later, splenic T cells were analyzed with enzyme-linked immunosorbent spot for HY immune response (n = 57). In subsequent experiments, mice were randomized into control (n = 7), RF ablation, ITDC (n = 9), and RF ablation + ITDC (n = 9) groups and monitored for tumor growth. Eleven days after treatment, tumors were harvested for histologic and immunohistochemical analysis. Animals demonstrating complete tumor regression were rechallenged in the contralateral flank.
  
  
  RESULTS
  Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression. RF ablation, ITDC, and combined groups demonstrated similar levels of antigen-presenting cell infiltration; all groups demonstrated greater levels of infiltration compared with untreated controls. ITDC injection also resulted in tumor regression. However, combination therapy did not enhance tumor regression when compared with either treatment alone. Rechallenged mice in RF ablation, ITDC, and combination groups demonstrated significant tumor growth inhibition compared with controls.
  
  
  CONCLUSIONS
  Subtotal RF ablation treatment results in enhanced systemic antitumor T-cell immune responses and tumor regression that is associated with increased dendritic cell infiltration. ITDC injection mimics the RF ablation effect but does not increase immune responses when injected immediately after RF ablation.
authors.affiliation: Diagnostic Radiology Department, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Dromi
authors.forename: Meghaan P
authors.initials: MP
authors.lastname: Walsh
authors.forename: Sarah
authors.initials: S
authors.lastname: Herby
authors.forename: Bryan
authors.initials: B
authors.lastname: Traughber
authors.forename: Jianwu
authors.initials: J
authors.lastname: Xie
authors.forename: Karun V
authors.initials: KV
authors.lastname: Sharma
authors.forename: Kiran P
authors.initials: KP
authors.lastname: Sekhar
authors.forename: Alfred
authors.initials: A
authors.lastname: Luk
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Fry
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D017115:Catheter Ablation; D045744:Cell Line, Tumor; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery*