Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

T cells but not NK cells are associated with a favourable outcome for resected colorectal liver metastases

Siân A Pugh1*, Rebecca J Harrison2, John N Primrose1 and Salim I Khakoo2

Author Affiliations

1 University Surgery, Southampton General Hospital, Southampton, UK

2 Department of Hepatology, Southampton General Hospital, Southampton, UK

For all author emails, please log on.

BMC Cancer 2014, 14:180  doi:10.1186/1471-2407-14-180

Published: 13 March 2014

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.

Keywords:
Natural Killer cells; Colorectal liver metastases; Innate immunity; Colorectal cancer; Adaptive immunity; T cells; CD56+ T cells