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 Kjaer

doi:10.3390/diagnostics3040344

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 Kjaer

Afdeling for Klinisk Fysiologi og Nuklearmedicin

29 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Diagnostics
Vol/bind	3
Udgave nummer	4
Sider (fra-til)	344-55
Antal sider	12
ISSN	2075-4418
DOI	https://doi.org/10.3390/diagnostics3040344
Status	Udgivet - 2 okt. 2013

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10.3390/diagnostics3040344

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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. ",

author = "Yin Wu and Pfeifer, {Andreas Klaus} and Rebecca Myschetzky and Garbyal, {Rajendra Singh} and Palle Rasmussen and Ulrich Knigge and Michael Bzorek and Kristensen, {Michael Holmsgaard} and Andreas Kjaer",

year = "2013",

month = oct,

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doi = "10.3390/diagnostics3040344",

language = "English",

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T1 - Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

AU - Wu, Yin

AU - Pfeifer, Andreas Klaus

AU - Myschetzky, Rebecca

AU - Garbyal, Rajendra Singh

AU - Rasmussen, Palle

AU - Knigge, Ulrich

AU - Bzorek, Michael

AU - Kristensen, Michael Holmsgaard

AU - Kjaer, Andreas

PY - 2013/10/2

Y1 - 2013/10/2

N2 - 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.

AB - 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.

U2 - 10.3390/diagnostics3040344

DO - 10.3390/diagnostics3040344

M3 - Journal article

C2 - 26824927

SN - 2075-4418

VL - 3

SP - 344

EP - 355

JO - Diagnostics

JF - Diagnostics

IS - 4

ER -

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

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