**5. Conclusions**

In conclusion, as shown in the scheme in Figure 7, we have provided translational evidence that miR-21-enriched GAM-derived exosomes contribute to GBM malignancy via increasing stemness. The feasibility of using pacritinib to modulate STAT3/miR-21/PDCD4 signaling was demonstrated using both in vitro and in vivo GBM models. Further investigation is warranted for conducting potential clinical trials for GBM patients experiencing TMZ resistance.

**Figure 7.** GAMs in the tumor microenvironment promote the survival of GBM cells via miR-21-enriched extracellular microvesicles (EVs). Mir-21 targets and suppresses the expression of tumor suppressor PDCD4 in GBM cells, leading to the elevated STAT3/Akt signaling. In turn, GBM cells secrete inflammatory cytokines TGF-β1 and IL-6 and promote M2 polarization. Pacritinib (STAT3 inhibitor) treatment suppresses GBM tumorigenesis by inhibiting STAT3 signaling and reducing M2 polarization of GAMs.
