title: Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response.
abstract: We have previously reported that intermediate monocytes (CD14(++)/CD16(+)) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14(+)/CD16(+) monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen.
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Dominic
authors.initials: D
authors.lastname: Schauer
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Starlinger
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Lejla
authors.initials: L
authors.lastname: Alidzanovic
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Zajc
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maier
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Feldman
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Robin
authors.initials: R
authors.lastname: Padickakudy
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Buchberger
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Elleder
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel, Vienna, Austria; Core Facility Flow Cytometry, Medical University of Vienna, General Hospital, Waehringer Guertel, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.affiliation: Department of Pathology, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Stift
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel , Vienna, Austria.
authors.forename: Lorand
authors.initials: L
authors.lastname: Pop
authors.affiliation: Department of Internal Medicine, Hospital of the Merciful Brothers , Johannes von Gott Platz 1 , Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Gruenberger
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel, Vienna, Austria; Department of Surgery I, Rudolf Foundation Clinic, Juchgasse, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gruenberger
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Waehringer Guertel, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
keywords: Bevacizumab; TIE2-expressing monocytes; intermediate monocytes; metastasized colorectal cancer; neoadjuvant chemotherapy