Treatment with subcutaneous heparin reduces myeloid-derived suppressor cells and enhances immune response in glioblastoma models, suggesting potential for improving immunotherapy.
Glioblastoma (GBM) derived extracellular vesicles (EVs) have been demonstrated to play a role in promoting and maintaining an immunosuppressive microenvironment. GBM-EVs contain bioactive molecules that can polarize immune cells towards an immunosuppressive phenotype including myeloid-derived suppressor cells (MDSCs). METHODS EVs were isolated using stepwise ultracentrifugation from mouse glioma cell lines (GL261 & SB28) 2D cultures and administered to mice via the retro-orbital route. The mice were then treated with subcutaneous heparin, which has been shown to disrupt the EV-cell binding at the interface preventing uptake. Total treatment duration was 2 weeks. Analysis of immune cellular populations was performed via flow cytometry. RESULTS Compared to sham (no EV) + heparin controls, EV + heparin treated mice showed a marginal decrease in thymic MDSCs (gMDSCs: 0.176% vs 0.089%; mMDSCs: 1.2% vs 0.95%), TIGIT+ expressing peripheral MDSCs (28% vs 10%), and peripheral Tregs (17.57% vs 5.01%). CONCLUSION Heparin may decrease the immunosuppressive effects of GBM-EVs by preventing the induction of immunosuppressive cell populations.
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Inocencio et al. (2025) studied this question.
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