title: Induction of Th1Immune responses following laser ablation in a murine model of colorectal liver metastases.
abstract: BACKGROUND
  Preliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may also stimulate host immunity against cancer. We investigated local and systemic induction of immune responses after laser ablation in the setting of residual tumor.
  
  
  METHODS
  A murine colorectal cancer (CRC) liver metastasis model was used. Selected tumors of liver CRC bearing mice and livers of mice without tumor induction were treated with LA. Liver and tumor tissues from the ablation sites and from distant sites were collected at various time points following LA and changes in CD3+ T cells and Kupffer cells (F4/80 marker) infiltration and the expression of interferon gamma (IFNγ) were investigated by immunohistochemistry and ELISpot. Base line levels of CD3+ T cells and Kupffer cells were established in untreated mice.
  
  
  RESULTS
  The presence of tumor induced significant accumulation of CD3+ T cells and Kupffer cells at the tumor-host interface, within the tumor vascular lakes and increased their baseline concentration within the liver parenchyma. LA of the liver induced accumulation of CD3+ T-cells and Kupffer cells at the site of injury and systemic induction of immune responses as discerned by the presence of IFNγ secreting splenocytes. LA of liver tumors induced significant increase of CD3+ T-cells at site of injury, within normal liver parenchyma, and the tumor-host interface of both ablated and distant tumors. In contrast Kupffer cells only accumulated in ablated tumors and the liver parenchyma but not in distant tumors. IFNγ expression increased significantly in ablated tumors and showed an increasing trend in distant tumors.
  
  
  CONCLUSIONS
  Laser ablation in addition to local tumor destruction induces local and systemic Th1 type immune responses which may play a significant role in inhibiting tumor recurrence from residual micrometastases or circulating tumor cells.
authors.affiliation: Department of Surgery, University of Melbourne, Austin Hospital, Heidelberg, Australia.
authors.forename: Wen Xu
authors.initials: WX
authors.lastname: Lin
authors.forename: Theodora
authors.initials: T
authors.lastname: Fifis
authors.forename: Caterina
authors.initials: C
authors.lastname: Malcontenti-Wilson
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nikfarjam
authors.forename: Vijayaragavan
authors.initials: V
authors.lastname: Muralidharan
authors.forename: Linh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Christopher
authors.initials: C
authors.lastname: Christophi
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D007109:Immunity / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology / Q000473:pathology; D053685:Laser Therapy; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000276:immunology* / Q000556:secondary* / Q000601:surgery; D008297:Male; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
chemical_list: D017252:CD3 Complex; D007371:Interferon-gamma