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L ow‐dose irradiated mesenchymal stromal cells break tumor defensive properties in vivo
Author(s) -
Stefani Francesca Romana,
Eberstål Sofia,
Vergani Stefano,
Kristiansen Trine A.,
Bengzon Johan
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31599
Subject(s) - mesenchymal stem cell , in vivo , cancer research , stromal cell , immune system , bone marrow , astrocytosis , radiation therapy , medicine , glioma , immunology , biology , pathology , immunohistochemistry , microbiology and biotechnology
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.