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

Research output: Contribution to journalArticle

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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • angiogenesis, glioma, immune modulation, MSC, TGFβ
Original languageEnglish
Pages (from-to)2200-2212
JournalInternational Journal of Cancer
Volume143
Issue number9
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes