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Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy

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Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tu...

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Main Authors: Klug, Felix (Author) , Prakash, Hridayesh (Author) , Huber, Peter E. (Author) , Seibel, Tobias Julian (Author) , Bender, Noemi (Author) , Halama, Niels (Author) , Pfirschke, Christina (Author) , Voß, Ralf-Holger (Author) , Timke, Carmen (Author) , Umansky, Ludmila (Author) , Klapproth, Kay (Author) , Schäkel, Knut (Author) , Garbi, Natalio (Author) , Jäger, Dirk (Author) , Weitz, Jürgen (Author) , Schmitz-Winnenthal, Friedrich Hubertus (Author) , Hämmerling, Günter J. (Author) , Beckhove, Philipp (Author)
Format: Article (Journal)
Language:English
Published: October 24, 2013
In: Cancer cell
Year: 2013, Volume: 24, Issue: 5, Pages: 589-602
ISSN:1878-3686
DOI:10.1016/j.ccr.2013.09.014
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ccr.2013.09.014
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1535610813004212
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Author Notes:Felix Klug, Hridayesh Prakash, Peter E. Huber, Tobias Seibel, Noemi Bender, Niels Halama, Christina Pfirschke, Ralf Holger Voss, Carmen Timke, Ludmila Umansky, Kay Klapproth, Knut Schäkel, Natalio Garbi, Dirk Jäger, Jürgen Weitz, Hubertus Schmitz-Winnenthal, Günter J. Hämmerling, and Philipp Beckhove
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Summary:Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models. LDI (local or pre-adoptive-transfer) programs the differentiation of iNOS+ M1 macrophages that orchestrate CTL recruitment into and killing within solid tumors through iNOS by inducing endothelial activation and the expression of TH1 chemokines and by suppressing the production of angiogenic, immunosuppressive, and tumor growth factors.
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Gesehen am 08.06.2022
Physical Description:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccr.2013.09.014

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