*4.2. Inhibitors of VEGF and PDGF Signaling*

VEGF-targeting agents such as sunitinib and cabozantinib can modulate the composition of immune cell subpopulations in the tumor and have been shown to enhance the efficacy of OV treatment. These agents, in combination with OVs, also act on several other aspects of the tumor adaptive immunity and TME, but mainly act through reducing the function of immunosuppressive cells, such as MDSCs, which in turn change cytokine levels (IL-1b, IL-6 and C-X-C motif chemokine ligand 1 (CXCL1)) and amplify the CD4<sup>+</sup> and CD8<sup>+</sup> -mediated tumor regression [109,110,117,246]. The molecular mechanism underlying this MDSC depletion is believed to relate to inhibition of STAT3, which blocks the development of immature myeloid cells into MDSCs, and VEGFR blockade, which results in a lower capacity of MDSCs to migrate to the TME [247].
