Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis

Fiona Hand, Cathal Harmon, Louise A. Elliott, Francesco Caiazza, Aonghus Lavelle, Donal Maguire, Emir Hoti, Niamh Nolan, Justin G. Geoghegan, Elizabeth J. Ryan, Cliona O’Farrelly

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. Methods: Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections. Results: Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM. Conclusions: The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

Original languageEnglish
Pages (from-to)1041-1052
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume67
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018
Externally publishedYes

Keywords

  • Colorectal liver metastases
  • Immune microenvironment
  • Leukocytes
  • Tumour progression

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