National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland.
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.
Cancer Immunol Immunother. 2018 Jul;67(7):1041-1052. doi: 10.1007/s00262-018-2149-5. Epub 2018 Mar 23.
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.
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.
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.
The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.
肝脏的免疫功能通常可抵抗肿瘤发生，但在结直肠癌肝转移（CRLM）中却被破坏。在这里，我们将 CRLM 患者肝脏组织的炎症微环境与供肝进行比较。
共招募了 25 例接受 CRLM 切除术的患者，其中 13 例在 18 个月内发生肝内复发。从肿瘤和肿瘤旁及远离肿瘤的正常肝组织中获取活检。在移植期间获取供肝活检。对活检进行培养并筛选条件培养基（CM）中的 102 种炎症介质。通过 Luminex 测定验证了其中 12 种。Transwell 测定法测量癌细胞趋化性。在 H&E 切片中定量中性粒细胞和淋巴细胞。
与供肝相比，转移性肝脏中门脉周围组织驻留的中性粒细胞较少。肿瘤远端肝脏中中性粒细胞最少的患者肝内复发的时间更短（P<0.001）。与供体组织相比，IL-6、CXCL1、CXCL5、G-CSF、GM-CSF、VEGF、LIF 和 CCL3 在携带 CRLM 的肝脏中更高。因此，癌细胞同样向转移性肝的所有区域的 CM 迁移，但不向供体肝 CM 迁移。
局部炎症环境可能影响免疫细胞浸润和癌细胞迁移，从而影响 CRLM 切除后的复发。
