Jan. 25, 2010 Immune cells known as myeloid-derived suppressor cells (MDSCs) keep other immune cells in check. They have been found to accumulate in individuals with cancer, where they are thought to contribute to tumor development.
François Ghiringhelli and colleagues, at INSERM U866, Dijon, France, have now identified a molecular pathway that enhances the immunosuppressive functions of tumor-associated mouse and human MDSCs.
In the study, tiny vesicles known as exosomes released by human and mouse tumor cells were found to have the molecule Hsp72 on their surface. This bound the protein TLR2 on human and mouse MDSCs, triggering a signaling pathway that resulted in enhanced MDSC suppressive function. Importantly, decreasing tumor exosome release pharmacologically in vivo enhanced the antitumor effects of the chemotherapeutic drug cyclophosphamide in three different mouse models of cancer.
The authors therefore suggest that drugs that prevent tumor exosome release might be beneficial to cancer patients being treated with conventional chemotherapeutic drugs.
The research appears in the Journal of Clinical Investigation.
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- Chalmin et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40483
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