TNF and neoplasm: In this sense, HEK 293 cell-derived EVs expressing hyaluronidase and coated with folic acid show a high accumulation in the tumor bed, where high-molecular-weight hyaluronic acid is degraded to low-molecular-weight hyaluronic acid, which is associated with the polarization of macrophages to an M1 phenotype, with the consequent modification of the TME, lowering the percentage of M2-TAMs and Treg cells and the expression of IL-4 and IL-10 and increasing the expression of TNF-α and IL-6 and the infiltration by Tc cells [151].