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

Francesca Romana Stefani, Sofia Eberstål, Stefano Vergani, Trine A. Kristiansen, Johan Bengzon

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

10 !!Citations (SciVal)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)2200-2212
TidskriftInternational Journal of Cancer
Volym143
Utgåva9
DOI
StatusPublished - 2018

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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