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

Stefani, Francesca Romana LU ; Eberstål, Sofia LU ; Vergani, Stefano LU ; Kristiansen, Trine A. LU and Bengzon, Johan LU (2018) In International Journal of Cancer 143(9). p.2200-2212
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
angiogenesis, glioma, immune modulation, MSC, TGFβ
in
International Journal of Cancer
volume
143
issue
9
pages
2200 - 2212
publisher
John Wiley & Sons
external identifiers
  • scopus:85053222669
  • pmid:29752716
ISSN
0020-7136
DOI
10.1002/ijc.31599
language
English
LU publication?
yes
id
5b56929e-9575-4d67-967e-e2a25271a808
date added to LUP
2018-10-22 12:20:57
date last changed
2020-03-24 06:26:33
@article{5b56929e-9575-4d67-967e-e2a25271a808,
  abstract     = {<p>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.</p>},
  author       = {Stefani, Francesca Romana and Eberstål, Sofia and Vergani, Stefano and Kristiansen, Trine A. and Bengzon, Johan},
  issn         = {0020-7136},
  language     = {eng},
  number       = {9},
  pages        = {2200--2212},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Low-dose irradiated mesenchymal stromal cells break tumor defensive properties in vivo},
  url          = {http://dx.doi.org/10.1002/ijc.31599},
  doi          = {10.1002/ijc.31599},
  volume       = {143},
  year         = {2018},
}