The limited capacity of malignant glioma-derived exosomes to suppress peripheral immune effectors

被引:30
作者
Iorgulescu, J. Bryan [1 ,2 ,3 ]
Ivan, Michael E. [1 ,4 ]
Safaee, Michael [1 ,2 ]
Parsa, Andrew T. [1 ,5 ]
机构
[1] UCSF, Dept Neurol Surg, San Francisco, CA USA
[2] UCSF, Clin & Translat Sci Inst, San Francisco, CA USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA
[4] Univ Miami, Dept Neurol Surg, Miami, FL USA
[5] Northwestern Feinberg Sch Med, Dept Neurol Surg, Chicago, IL USA
关键词
Glioma; Exosome; Microvesicle; Immunosuppression; Immunotherapy; T-CELLS; GLIOBLASTOMA-MULTIFORME; B7-H1; EXPRESSION; SHOCK PROTEINS; MYELOID CELLS; REGULATORY T; MICROVESICLES; IMMUNOTHERAPY; IMMUNOSUPPRESSION; PROMOTE;
D O I
10.1016/j.jneuroim.2015.11.025
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Tumor-derived microvesicular exosomes permit intercellular communication both locally and systemically by delivering a snapshot of the tumor cell's constituents. We thus investigated whether exosomes mediate malignant glioma's facility for inducing peripheral immunosuppression. In Western blot and RT-PCR analyses, glioma-derived exosomes displayed exosome-specific markers, but failed to recapitulate the antigen presentation machinery, surface co-modulatory signals, or immunosuppressive mediator status of their parent tumor cells. Treatment with glioma-derived exosomes promoted immunosuppressive HLA-DRlow monocytic phenotypes, but failed to induce monocytic PD-L1 expression or alter the activation of cytotoxic T-cells from patients' peripheral blood by FACS and RT-PCR analyses. Our results suggest that malignant glioma-derived exosomes are restricted in their capacity to directly prime peripheral immunosuppression. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:103 / 108
页数:6
相关论文
共 43 条
[1]
Mechanisms of Local Immunoresistance in Glioma [J].
Albesiano, Emilia ;
Han, James E. ;
Lim, Michael .
NEUROSURGERY CLINICS OF NORTH AMERICA, 2010, 21 (01) :17-+
[2]
Exosomes as potent cell-free peptide-based vaccine.: I.: Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells [J].
André, F ;
Chaput, N ;
Schartz, NEC ;
Flament, C ;
Aubert, N ;
Bernard, J ;
Lemonnier, F ;
Raposo, G ;
Escudier, B ;
Hsu, DH ;
Tursz, T ;
Amigorena, S ;
Angevin, E ;
Zitvogel, L .
JOURNAL OF IMMUNOLOGY, 2004, 172 (04) :2126-2136
[3]
Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling [J].
Bendz, Henriette ;
Ruhland, Sibylle C. ;
Pandya, Maya J. ;
Hainzl, Otmar ;
Riegelsberger, Stefan ;
Braeuchle, Christoph ;
Mayer, Matthias P. ;
Buchner, Johannes ;
Issels, Rolf D. ;
Noessner, Elfriede .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (43) :31688-31702
[4]
Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial [J].
Bloch, Orin ;
Crane, Courtney A. ;
Fuks, Yelena ;
Kaur, Rajwant ;
Aghi, Manish K. ;
Berger, Mitchel S. ;
Butowski, Nicholas A. ;
Chang, Susan M. ;
Clarke, Jennifer L. ;
McDermott, Michael W. ;
Prados, Michael D. ;
Sloan, Andrew E. ;
Bruce, Jeffrey N. ;
Parsa, Andrew T. .
NEURO-ONCOLOGY, 2014, 16 (02) :274-279
[5]
Gliomas Promote Immunosuppression through Induction of B7-H1 Expression in Tumor-Associated Macrophages [J].
Bloch, Orin ;
Crane, Courtney A. ;
Kaur, Rajwant ;
Safaee, Michael ;
Rutkowski, Martin J. ;
Parsa, Andrew T. .
CLINICAL CANCER RESEARCH, 2013, 19 (12) :3165-3175
[6]
Extracellular Vesicles Modulate the Glioblastoma Microenvironment via a Tumor Suppression Signaling Network Directed by miR-1 [J].
Bronisz, Agnieszka ;
Wang, Yan ;
Nowicki, Michal O. ;
Peruzzi, Pierpaolo ;
Ansari, Khairul I. ;
Ogawa, Daisuke ;
Balaj, Leonora ;
De Rienzo, Gianluca ;
Mineo, Marco ;
Nakano, Ichiro ;
Ostrowski, Michael C. ;
Hochberg, Fred ;
Weissleder, Ralph ;
Lawler, Sean E. ;
Chiocca, E. Antonio ;
Godlewski, Jakub .
CANCER RESEARCH, 2014, 74 (03) :738-750
[7]
Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma [J].
Bu, Ning ;
Wu, Haiqin ;
Sun, Bingzhong ;
Zhang, Guilian ;
Zhan, Shuqin ;
Zhang, Ru ;
Zhou, Le .
JOURNAL OF NEURO-ONCOLOGY, 2011, 104 (03) :659-667
[8]
Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells [J].
Chalmin, Fanny ;
Ladoire, Sylvain ;
Mignot, Gregoire ;
Vincent, Julie ;
Bruchard, Melanie ;
Remy-Martin, Jean-Paul ;
Boireau, Wilfrid ;
Rouleau, Alain ;
Simon, Benoit ;
Lanneau, David ;
De Thonel, Aurelie ;
Multhoff, Gabriele ;
Hamman, Arlette ;
Martin, Francois ;
Chauffert, Bruno ;
Solary, Eric ;
Zitvogel, Laurence ;
Garrido, Carmen ;
Ryffel, Bernhard ;
Borg, Christophe ;
Apetoh, Lionel ;
Rebe, Cedric ;
Ghiringhelli, Francois .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (02) :457-471
[9]
Microfluidic isolation and transcriptome analysis of serum microvesicles [J].
Chen, Chihchen ;
Skog, Johan ;
Hsu, Chia-Hsien ;
Lessard, Ryan T. ;
Balaj, Leonora ;
Wurdinger, Thomas ;
Carter, Bob S. ;
Breakefield, Xandra O. ;
Toner, Mehmet ;
Irimia, Daniel .
LAB ON A CHIP, 2010, 10 (04) :505-511
[10]
MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models [J].
Cho, Jung-ah ;
Lee, Yeong-Shin ;
Kim, Soo-Hyun ;
Ko, Jin-Kyung ;
Kim, Chul-Woo .
CANCER LETTERS, 2009, 275 (02) :256-265