title: T cells but not NK cells are associated with a favourable outcome for resected colorectal liver metastases.
abstract: BACKGROUND
  The adaptive immune response to colorectal cancer is important for survival. Less is understood about the role of innate lymphocytes, such as Natural Killer (NK) cells, which are abundant in human liver.
  
  
  METHODS
  Samples of fresh liver (n = 21) and tumour (n = 11) tissue were obtained from patients undergoing surgical resection of colorectal liver metastases. Flow cytometry was used to analyse the presence and phenotype of NK cells, as compared to T cells, in the tumour and liver tissue. Results were correlated with survival.
  
  
  RESULTS
  NK cells were poorly recruited to the tumours (distant liver tissue 38.3%, peritumoural liver 34.2%, tumour 12.9%, p = 0.0068). Intrahepatic and intratumoural NK cells were KIR (killer immunoglobulin-like receptor)loNKG2Ahi whereas circulating NK cells were KIRhiNKG2Alo. By contrast T cells represented 65.7% of the tumour infiltrating lymphocytes. Overall survival was 43% at 5 years, with the 5-year survival for individuals with a T cell rich infiltrate being 60% (95% CI 17-93%) and for those with a low T cell infiltrate being 0% (95% CI 0-48%). Conversely individuals with higher levels of NK cells in the tumour had an inferior outcome, although there were insufficient numbers to reach significance (median survivals: NKHi 1.63 years vs NKLo 3.92 years).
  
  
  CONCLUSIONS
  T cells, but not NK cells, are preferentially recruited to colorectal liver metastases. NK cells within colorectal metastases have an intrahepatic and potentially tolerogenic, rather than a peripheral, phenotype. Similar to primary tumours, the magnitude of the T cell infiltrate in colorectal metastases is positively associated with survival.
authors.affiliation: University Surgery, Southampton General Hospital, Southampton, UK. S.Pugh@soton.ac.uk.
authors.forename: Siân A
authors.initials: SA
authors.lastname: Pugh
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Harrison
authors.forename: John N
authors.initials: JN
authors.lastname: Primrose
authors.forename: Salim I
authors.initials: SI
authors.lastname: Khakoo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary* / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D016896:Treatment Outcome