The link between CXCL9 and tumour infiltration of lymphoid populations in liver metastases


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Dalal Almuaili1,Fiona Hand2,Cathal Harmon1,Elizabeth Ryan3,Niamh Nolan2,Justin Geoghegan2,Cliona O’Farrelly1
1trinity college dublin,2St Vincent's university hospital,3university college dublin

Abstract

Background

A significant proportion of colorectal cancer patients develop liver metastases (CRLM) despite its potent anti-tumour properties. The healthy liver is maintained by immune populations that are recruited, regulated and controlled by a local cytokine microenvironment including the lymphoid populations’ chemokine CXCL9.

We propose that a dysregulation of the liver cytokine microenvironment compromises its defense and increases its metastatic susceptibility. We aim to investigate changes in immune T-cell populations and levels of CXCL9 in the livers of CRLM patients. 

Method

Tumour and tumour adjacent liver biopsies were collected from patients undergoing resection for CRLM [N=18] and from donor livers [N=10]. Portions were paraffin embedded for immunohistochemistry and stained for CD45 (immune cells marker), and CD3 (T cell marker), and homogenised for total protein extraction.

Results

Immunohistochemistry demonstrated T cell populations throughout the liver parenchyma with aggregations around portal triads in donor liver (p=0.001).  Immune populations aggregated around the edges of tumours, and were excluded from the tumour tissue. Significantly higher T-cell numbers (p=0.04) and lower leukocyte numbers were evident in tumours compared to donors. CXCL9 was significantly higher in tumour tissue (p=0.009) compared to donor. We demonstrate a wide spectrum of leukocytes and T cells in CRLM tissue with two different patterns of infiltration correlating with expression of CXCL9.

Conclusion

T-cell infiltration has been previously linked to survival. We demonstrate similar patterns of immune infiltration, and CXCL9 expression suggesting a link. The Identification of specific factors or the microenvironmental signature responsible for immune infiltration could provide a novel target for immune therapy.