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Updated: Apr 3, 2026
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Glioma-derived extracellular vesicles selectively suppress immune responses
Justin E Hellwinkel1, Jasmina S Redzic1, Tessa A Harland1
1Dept of Neurosurgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado (J.E.H, T.A.H, D.G., M.W.G); Skaggs School of Pharmacy, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado (J.S.R, T.J.A).
Background:
Glioma-related immunosuppression is well documented; however, the mechanisms of suppression are not fully understood. Here we explore a role for glioma extracellular vesicles (EVs) as a means of immune modulation.
Methods:
Healthy donor peripheral blood mononuclear cells (PBMCs) were incubated with mitogenic stimuli and various concentrations of glioma-derived EVs. Intracellular signaling and cytokine output were determined by protein microarrays, and phenotypic changes were assessed by flow cytometry. Recall antigen testing, mixed lymphocyte reactions, and migration assays analyzed PBMC functional capacity.
Results:
Protein microarray data revealed induction of an immunosuppressive phenotype and cytokine output at high tumor-vesicle concentrations but an activated phenotype at low concentrations. T cell activation antigen expression confirmed differential activation profiles. Functional analyses revealed decreased migratory capacity of PBMCs after incubation with EVs; however, recall antigen and mixed lymphocyte tests indicated that activation capacity is still retained in EV-treated cells.
Conclusion:
The differential effects of high and low EV concentrations dictate modulatory effects on PBMCs. These data provide a role for EVs at high concentrations for inducing selective tolerance of an immune response in a tumor setting. This suggests that lymphocytes in patients' circulation are not irreparably impaired, as previously thought, but can be rescued to augment antitumor responses.
Insights
Glioma extracellular vesicles (EVs) modulate immune cells. High EV concentrations induce immunosuppression, while low concentrations activate immune cells, suggesting potential for rescuing antitumor responses.
Area of Science:
- Immunology
- Oncology
- Extracellular Vesicle Biology
Background:
- Glioma-associated immunosuppression mechanisms are not fully understood.
- Extracellular vesicles (EVs) derived from gliomas may play a role in immune modulation.
Purpose of the Study:
- To investigate the immunomodulatory effects of glioma-derived EVs on peripheral blood mononuclear cells (PBMCs).
- To determine the impact of varying EV concentrations on immune cell phenotype and function.
Main Methods:
- Incubation of human PBMCs with glioma-derived EVs.
- Analysis of intracellular signaling and cytokine output using protein microarrays.
- Assessment of PBMC phenotypic changes via flow cytometry.
- Evaluation of PBMC functional capacity through recall antigen testing, mixed lymphocyte reactions, and migration assays.
Main Results:
- High concentrations of glioma EVs induced an immunosuppressive phenotype and cytokine output in PBMCs.
- Low concentrations of glioma EVs promoted an activated PBMC phenotype.
- EVs reduced PBMC migratory capacity but retained their activation capacity in recall antigen and mixed lymphocyte tests.
Conclusions:
- Differential effects of high and low EV concentrations on PBMCs dictate immune response modulation.
- High concentrations of glioma EVs can induce selective immune tolerance in a tumor microenvironment.
- Lymphocytes in patients are not irreparably impaired and can be potentially rescued to enhance antitumor responses.
