期刊
ONCOIMMUNOLOGY
卷 7, 期 4, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1412909
关键词
cancer stem cells; exosome; glioblastoma; immune cells; STAT3; PD-L1
资金
- Anthony Bullock III Foundation
- Cynthia and George Mitchell Foundation
- Dr. Marnie Rose Foundation
- Ben and Catherine Ivy Foundation
- Provost Retention Fund
- National Institutes of Health [CA1208113, P50 CA127001, P50 CA093459]
- NIH through The University of Texas MD Anderson Cancer Center [P30 CA016672]
- Cancer Prevention Research Institute of Texas [RP130397]
- NIH [1S10OD012304-01, 1S10RR029552]
- NATIONAL CANCER INSTITUTE [P30CA016672] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS097649] Funding Source: NIH RePORTER
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.
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