Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy - PubMed (original) (raw)
. 2013 Nov 11;24(5):589-602.
doi: 10.1016/j.ccr.2013.09.014. Epub 2013 Oct 24.
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, Philipp Beckhove
Affiliations
- PMID: 24209604
- DOI: 10.1016/j.ccr.2013.09.014
Free article
Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy
Felix Klug et al. Cancer Cell. 2013.
Free article
Abstract
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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Comment in
- A new twist on radiation oncology: low-dose irradiation elicits immunostimulatory macrophages that unlock barriers to tumor immunotherapy.
De Palma M, Coukos G, Hanahan D. De Palma M, et al. Cancer Cell. 2013 Nov 11;24(5):559-61. doi: 10.1016/j.ccr.2013.10.019. Cancer Cell. 2013. PMID: 24229704
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