Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells

Academic Article

Abstract

  • In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-α than MDSCs isolated from the lung of MyD88 KO mice. In vitro, addition of tumor exosomes to bone marrow-derived CD11b+ Gr-1+ cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-α, interleukin-6, and the chemokine CCL2, than CD11b +Gr-1+ cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis. Copyright © American Society for Investigative Pathology.
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    Digital Object Identifier (doi)

    Author List

  • Liu Y; Xiang X; Zhuang X; Zhang S; Liu C; Cheng Z; Michalek S; Grizzle W; Zhang HG
  • Start Page

  • 2490
  • End Page

  • 2499
  • Volume

  • 176
  • Issue

  • 5