Louisville, KY – Current research suggests that tumor-secreted exosomes inhibit the immune response, enhancing tumor metastasis. The related report by Liu et al, "Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells," appears in the May 2010 issue of The American Journal of Pathology.
The immune system plays a critical role in identifying and destroying tumor cells. Many tumors overcome this surveillance by inhibiting local immune responses, often leading to metastasis.
One potential method of tumor-mediated immune suppression is secretion of exosomes - small, membrane-enclosed sacs that can be used for storage or transport. Researchers led by Dr. Huang-Ge Zhang and colleagues at the University of Alabama at Birmingham and the University of Louisville, KY therefore examined the effect of tumor-secreted exosomes in lung metastasis. They found that treatment with tumor exosomes increased the number of myeloid-derived suppressor cells, which inhibited immune activation and accelerated tumor metastasis in the lung. This effect was mediated by the molecule MyD88, which plays a key role in the innate immune response.
In this study, Liu et al "identified the role of tumor exosomes in the enhancement of tumor metastasis through the expansion of myeloid-derived suppressor cells. A tremendous amount of information remains to be discovered about the mechanisms of cellular machinery that regulates the sorting of immune suppressor molecules into tumor exosomes. [Their] goal will now be to develop not only strategies to interfere with these pathways, but to transform tumor exosomes from immune suppressors to immune stimuli with the objective to ultimately use these modified exosomes as a tumor vaccine."
This work was supported by grants from National Institutes of Health (NIH) (RO1CA116092, RO1CA107181, R01AT004294, R01CA137037); Birmingham Veterans Administration Medical Center (VAMC) Merit Review Grants (H.-G.Z.); and a grant from the Susan G. Komen Breast Cancer Foundation.
Liu Y, Xiang X, Zhuang X, Zhang X, Liu C, Cheng Z, Michalek S, Grizzle W, Zhang H-G: Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. Am J Pathol 2010, 176: 2490-2499
For more information on Dr Huang-Gu Zhang, please contact Lauren R. Williams, Senior Public Relations Specialist, University of Louisville, Health Sciences Campus, Office of Communications & Marketing, Phone: (502) 852-7461, E-mail: Lauren.Williams@louisville.edu. .
For press copies of the articles, please contact Dr. Angela Colmone at 301-634-7953 or acolmone@asip.org.
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.
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American Journal Of Pathology