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Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is associated with the tumor-immune microenvironment. To evaluate the characteristics of vascular and tumor cells in chordoma, we first analyzed the expression of VEGF receptor (VEGFR) 1, VEGFR2, CD34, and Brachyury in a cell line and 54 tumor tissues. Patients with primary skull base chordomas were divided into the two groups as per the tumor growth rate. The expressions of VEGF-A, VEGFR1, and VEGFR2 on tumor cells; tumor infiltrative immune cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs); and immune-checkpoint molecules (PD-1/PD-L1) were analyzed with the clinical courses. Both VEGFR1 and VEGFR2 were strongly expressed not only on vascular endothelial cells, but also on tumor cells. The recurrent cases showed significantly higher VEGFR1 expressions on tumor cells than the primary cases. The expression of VEGF-A, and the numbers of CD163+ TAMs and Foxp3+ Tregs were significantly higher in the patients with rapid progressive course than the patients with slow progressive course. Based on the present results, VEGFRs-targeted therapy may show efficacy in regulating growth of chordomas.

IMT-02 VEGF RECEPTORS EXPRESSION AND REPORT OF CLINICAL TRIAL OF PEPTIDE VACCINE IN SKULL BASE CHORDOMA