title: Preoperative granulocyte/macrophage colony-stimulating factor (GM-CSF) increases hepatic dendritic cell numbers and clustering with lymphocytes in colorectal cancer patients.
abstract: Despite surgery with curative intent, approximately 30% of colorectal carcinoma patients will develop liver metastases during follow-up. Synchronous occult micrometastases, tumor cell shedding into the portal circulation and postoperative immune impairment have all been suggested to facilitate outgrowth of liver metastases. In experimental models, increases in both number of resident macrophages of the liver, the so-called Kupffer cells (KC), and tumoricidal capacity of KC were observed after pretreatment with granulocyte/macrophage colony-stimulating factor (GM-CSF), a potent immuno-stimulatory agent. Following perioperative recombinant human GM-CSF (rhGM-CSF), we previously showed activation of the systemic immune response in the postoperative period, which is normally transiently down-modulated after surgery. Therefore, in this pilot study, effects of preoperative rhGM-CSF administration on the composition of human liver immune cell population were evaluated in patients undergoing surgery for colorectal cancer. No difference in KC numbers of rhGM-CSF-treated patients was observed. Importantly, however, a 6-fold increase in dendritic cell (DC) numbers was observed compared to control patients, as quantified by immunohistochemistry of liver biopsies, taken during laparotomy. Furthermore, direct contact between liver CD8+ cells and DC was significantly enhanced in rhGM-CSF-treated patients. Both increases in DC numbers and DC interaction with CD8+ T cells suggest enhanced immunological activation, which may reduce liver metastases formation and ultimately improve survival after initial colorectal surgery.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Oosterling
authors.forename: Anneke K
authors.initials: AK
authors.lastname: Mels
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Gerben J
authors.initials: GJ
authors.lastname: van der Bij
authors.forename: Cornelis W
authors.initials: CW
authors.lastname: Tuk
authors.forename: Ronald J C L M
authors.initials: RJ
authors.lastname: Vuylsteke
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor