title: Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.
abstract: BACKGROUND
  Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol-paravertebral block (PPA) or sevoflurane-opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500).
  
  
  METHODS
  Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA (n=5) and GA (n=5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined.
  
  
  RESULTS
  Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 [from mean (sem), 82 (2)% to 50 (4)%, P=0.001], IL-10 [from 1700 (80) to 1200 (92) pg ml(-1), P=0.001], and IL-1β [from 68 (12) to 19 (4) pg ml(-1), P=0.01]. An increase in NK cell CD107a [23 (2)% to 37(3)%, P=0.007] and apoptosis of HCC1500 [11 (1)% to 21 (2)%, P=0.0001] was observed with PPA serum, but not GA serum, treated NK cells.
  
  
  CONCLUSIONS
  Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA.
  
  
  BACKGROUND
  NCT 041857.
authors.affiliation: Department of Anaesthesia, Mater Misericordiae University Hospital, Dublin, Ireland buckleyaisling@hotmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Department of Immunology, Dublin City University, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: McQuaid
authors.affiliation: Department of Immunology, Dublin City University, Dublin, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: Johnson
authors.affiliation: Department of Anaesthesia, Mater Misericordiae University Hospital, Dublin, Ireland School of Medicine & Medical Science, University College Dublin, Dublin, Ireland Outcomes Research Consortium, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Buggy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia / Q000379:methods*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods; D010865:Pilot Projects; D015742:Propofol / Q000494:pharmacology; D000077149:Sevoflurane; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol
keywords: anaesthesia regional; anaesthesia, general; breast neoplasms; immune cells, natural killer cells; immunity, innate