Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study

Br J Anaesth. 2014 Jul;113 Suppl 1:i56-62. doi: 10.1093/bja/aeu200. Epub 2014 Jul 9.

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.

Conclusion: 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.

Clinical trial registration: NCT 041857.

Trial registration: ClinicalTrials.gov NCT00418457.

Keywords: anaesthesia regional; anaesthesia, general; breast neoplasms; immune cells, natural killer cells; immunity, innate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anesthesia / methods*
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / blood
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Coculture Techniques
  • Female
  • Humans
  • Immunity, Innate / drug effects
  • Killer Cells, Natural / drug effects*
  • Methyl Ethers / pharmacology
  • Middle Aged
  • Nerve Block / methods
  • Pilot Projects
  • Propofol / pharmacology
  • Sevoflurane
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Methyl Ethers
  • Sevoflurane
  • Propofol

Associated data

  • ClinicalTrials.gov/NCT00418457