title: Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor.
abstract: Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that (177)Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.
authors.affiliation: Peter Gorer Department of Immunobiology, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK. yin.wu@kcl.ac.uk.|Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. yin.wu@kcl.ac.uk.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. andreas.pfeifer@mac.com.
authors.forename: Andreas Klaus
authors.initials: AK
authors.lastname: Pfeifer
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. rebeccam@mfi.ku.dk.|Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark. rebeccam@mfi.ku.dk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Myschetzky
authors.affiliation: Department of Clinical Pathology, Næstved Hospital, Ringstedgade 61, Naestved, 4700, Denmark. raje@regionsjaelland.dk.
authors.forename: Rajendra Singh
authors.initials: RS
authors.lastname: Garbyal
authors.affiliation: Risø National Laboratory, Danish Technical University, Anker Engelunds Vej 1, Lyngby, 2100, Denmark. pall@dtu.dk.
authors.forename: Palle
authors.initials: P
authors.lastname: Rasmussen
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. ulrich.peter.knigge@regionh.dk.|Department of Surgery C, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark. ulrich.peter.knigge@regionh.dk.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Knigge
authors.affiliation: Department of Clinical Pathology, Næstved Hospital, Ringstedgade 61, Naestved, 4700, Denmark. mibz@regionsjaelland.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Bzorek
authors.affiliation: Department of Clinical Pathology, Næstved Hospital, Ringstedgade 61, Naestved, 4700, Denmark. mick@regionsjaelland.dk.
authors.forename: Michael Holmsgaard
authors.initials: MH
authors.lastname: Kristensen
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. akjaer@sund.ku.dk.|Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark. akjaer@sund.ku.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
keywords: 177Lu-DOTATATE; CD49b+; CD86+; FasL+; NK cells; PRRT; dendritic cells
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