Figure 8.

The schematic diagram adapted from “Modulation of Tumor Blood Vessels”, by BioRender.com (2023) and retrieved from https://app.biorender.com/biorender-templates of dose-escalating lenvatinib to enhance vascular normalization and elevated the efficacy of ICBs. The tumor cells secret different kinds of growth factors such as VEGF, PDGF and FGF to promote angiogenesis, which results in the structural abnormalities of tumor vasculature. The low-dose lenvatinib fails to effectively inhibit the abnormal angiogenesis so there are still numerous dysfunctional vessels to limit the transportation of oxygen and drugs. The adequate-dose lenvatinib effectively prune the abnormal vessels and promoted the normalization of the remaining, which improves the immunosuppressive TME and elevated the efficacy of ICBs. The high-dose lenvatinib excessively prunes the functional vessels inside the tumor and results in the shortage of blood supply, which aggravates the hypoxia and perfusion.