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

Authors :
Stefani FR
Eberstål S
Vergani S
Kristiansen TA
Bengzon J
Source :
International journal of cancer [Int J Cancer] 2018 Nov 01; Vol. 143 (9), pp. 2200-2212. Date of Electronic Publication: 2018 Aug 07.
Publication Year :
2018

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 astrocytosis and display anti-angiogenic properties. Hence, the present study provides strong evidence for a therapeutic potential of low-dose irMSCs in cancer as well as giving new insight into MSC biology and applications.<br /> (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Details

Language :
English
ISSN :
1097-0215
Volume :
143
Issue :
9
Database :
MEDLINE
Journal :
International journal of cancer
Publication Type :
Academic Journal
Accession number :
29752716
Full Text :
https://doi.org/10.1002/ijc.31599