Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

Yin Wu, Andreas Klaus Pfeifer, Rebecca Myschetzky, Rajendra Singh Garbyal, Palle Rasmussen, Ulrich Knigge, Michael Bzorek, Michael Holmsgaard Kristensen, Andreas Kjær

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    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 177Lu-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.
    Original languageEnglish
    JournalDiagnostics
    Volume3
    Issue number4
    Pages (from-to)344-55
    Number of pages12
    ISSN2075-4418
    DOIs
    Publication statusPublished - 2013

    Keywords

    • 177Lu-DOTATATE
    • CD49b+
    • CD86+
    • FasL+
    • NK Cells
    • PRRT
    • Dendritic Cells

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