Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes

OncoImmunology

Shouhao Zhou¹  Raghu Kalluri²  Kenneth Dunner²  Johnny C. Akers³  Clark Chen³  Felix Nwajei⁴  M. Anna Zal⁴  Tomasz Zal⁴  Xu Li⁵  Aras Rezavanian⁶  Changiz Geula⁶  Jared K. Burks⁷  Jack P. Antel⁸  Luke M. Healy⁸  Jason T. Huse⁹  Gregory N. Fuller⁹  Sourindra N. Maiti^1,10  Laurence Cooper^1,10  Shulin Li^1,10  Erik P. Sulman^1,11  David Hawke^1,12  Joy Gumin^1,13  Yuuri Hashimoto^1,13  Anwar Hossain^1,13  Jun Wei^1,13  Konrad Gabrusiewicz^1,13  Anantha L. Marisetty^1,13  John Yu^1,13  Shinji Yamashita^1,13  Martina Ott^1,13  Yuzaburo Shimizu^1,13  Raymond Sawaya^1,13  Ganesh Rao^1,13  Fei Wang^1,13  Amy B. Heimberger^1,13 

[1] Biostatistics, The University of Texas MD Anderson Cancer Center;Cancer Biology, The University of Texas MD Anderson Cancer Center;Center for Theoretical and Applied Neuro-Oncology, University of California;Immunology, The University of Texas MD Anderson Cancer Center;Institute of Biology, Westlake Institute for Advanced Study, Westlake University;Laboratory for Cognitive and Molecular Morphometry, Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Feinberg School of Medicine;Leukemia, The University of Texas MD Anderson Cancer Center;Montreal Neurological Institute and Hospital, McGill University;Neuropathology, The University of Texas MD Anderson Cancer Center;Pediatrics, The University of Texas MD Anderson Cancer Center;Radiation Oncology, The University of Texas MD Anderson Cancer Center;Systems Biology, The University of Texas MD Anderson Cancer Center;The University of Texas MD Anderson Cancer Center;

关键词: cancer stem cells;    exosome;    glioblastoma;    immune cells;    stat3;    pd-l1;   

DOI  :  10.1080/2162402X.2017.1412909

来源: DOAJ

【 摘 要 】

Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14+ cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.

【 授权许可】

Unknown