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

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

Cancer Immunol Immunother

School of Biochemistry and Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, 154-160 Pearse Street, Dublin 2, D02 R590, Ireland.

Published: July 2018

AI Article Synopsis

  • The study investigates how the immune response in the liver is altered in patients with colorectal liver metastasis (CRLM), comparing it to healthy donor liver tissue.
  • It analyzes liver biopsies from 25 patients undergoing surgery, focusing on inflammatory mediators and the presence of immune cells.
  • Results show a significant reduction in a type of immune cell (PMN) in metastatic liver tissue, which correlates with faster cancer recurrence, indicating that the inflammatory environment influences both immune response and cancer cell movement.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11028161PMC
http://dx.doi.org/10.1007/s00262-018-2149-5DOI Listing

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