Low-dose irradiated mesenchymal stromal cells break tumor defensive properties in vivo

International Journal of Cancer. Journal International Du Cancer
Francesca Romana StefaniJohan Bengzon

Abstract

Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies to overcome tumor resistance are mainly represented by multi-targeted approaches, and cell vector-based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow-derived mesenchymal stromal cells (MSCs), when primed with low-dose irradiation (irMSCs), undergo changes in their immunogenic and angiogenic capacity and acquire anti-tumoral properties in a mouse model of glioblastoma (GBM). Following grafting in GL261 glioblastoma, irMSCs migrate extensively and selectively within the tumor and infiltrate predominantly the peri-vascular niche, leading to rejection of established tumors and cure in 29% of animals. The therapeutic radiation dose window is narrow, with effects seen between 2 and 15 Gy, peaking at 5 Gy. A single low-dose radiation decreases MSCs inherent immune suppressive properties in vitro as well as shapes their immune regulatory ability in vivo. Intra-tumorally grafted irMSCs stimulate the immune system and decrease immune suppression. Additionally, irMSCs enhance peri-tumoral reactive as...Continue Reading

References

May 4, 2000·The New England Journal of Medicine·G C BlobeH F Lodish
Jun 5, 2002·The Journal of Experimental Medicine·Leonid GorelikRichard A Flavell
Apr 19, 2005·Cancer Research·Akira NakamizoFrederick F Lang
Apr 23, 2005·Glia·Milos Pekny, Michael Nilsson
Oct 21, 2006·Current Opinion in Hematology·Armand Keating
Mar 1, 2007·Blood·Ainhoa Perez-DiezPolly Matzinger
Jul 24, 2007·Nature Reviews. Neuroscience·Rakesh K JainTracy T Batchelor
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephen H WrzesinskiRichard A Flavell
Jun 4, 2008·Future Oncology·Eleanor A VegaJohn H Sampson
Nov 6, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel BexellJohan Bengzon
Feb 7, 2009·Nature Reviews. Immunology·Dmitry I Gabrilovich, Srinivas Nagaraj
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Seth B CoffeltAline B Scandurro
Jun 3, 2010·Cold Spring Harbor Protocols·Donald C RioTimothy W Nilsen
Aug 25, 2012·Bioscience Reports·Qiaoshu WangTao Zhang
Nov 21, 2012·Immunology and Cell Biology·Tara SugrueRhodri Ceredig
Jun 26, 2013·Immunology and Cell Biology·Yazan S KhaledEyad Elkord
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Nov 5, 2013·Cell Death and Differentiation·S MaY Wang
Dec 20, 2013·International Journal of Radiation Oncology, Biology, Physics·Nils H NicolayPeter E Huber
Apr 30, 2014·Cancer Immunology Research·Hye-Jung Kim, Harvey Cantor
Oct 24, 2014·Frontiers in Immunology·Anita C Thomas, Joshua T Mattila
Nov 27, 2014·Journal of Radiation Research·Mohammad S IslamSusanta K Hui
Dec 3, 2014·Pharmacology & Therapeutics·Cindy NeuzilletArmand de Gramont
Jul 4, 2015·Cell Stem Cell·Alan Trounson, Courtney McDonald
Oct 17, 2015·Nature Reviews. Immunology·Shannon J TurleyJillian L Astarita
Jul 7, 2016·Nature Communications·Vincenzo BronteDmitry I Gabrilovich
Oct 18, 2016·Cytotherapy·Elizabeth K SageSam M Janes
Nov 5, 2016·Nature Reviews. Drug Discovery·Yufang ShiYing Wang
Jan 12, 2017·Acta Neuropathologica·Krissie LentingWilliam Leenders
Feb 9, 2017·Stem Cells Translational Medicine·Stephanie J Marfy-Smith, Claire E Clarkin

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Citations

Dec 26, 2018·International Journal of Radiation Biology·Yi WangDmitry Klokov
Nov 19, 2019·International Journal of Radiation Oncology, Biology, Physics·Zijian DengKen Kang-Hsin Wang
Nov 19, 2020·Stem Cell Reviews and Reports·Amanda Nogueira-PedroRicardo Ambrósio Fock
Jun 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Blazej NowakAnna Andrzejewska
Aug 15, 2021·The International Journal of Biochemistry & Cell Biology·Xinqi GeQianqian Liu
May 26, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Jennifer Alexander, Edna Cukierman

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

FlowJo
GraphPad
Visiopharm stereology
GraphPad Prism

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