Yukina Morimoto1, Ryota Tamura1, Kentaro Ohara2, Kenzo Kosugi1, Yumiko Oishi1, Yuki Kuranari1, Kazunari Yoshida1, Masahiro Toda3. 1. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 2. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 3. Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. todam@keio.jp.
Abstract
BACKGROUND: Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is strongly associated with the tumor-immune microenvironment. These factors have not been elucidated for chordomas. METHODS: 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 following two groups as per the tumor growth rate: patients with slow progression (SP: < 3 mm/year) and those with rapid progression (RP: ≥ 3 mm/year). Thus, the expressions of VEGF-A, VEGFR 1, 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, especially in a comparison between the two groups. RESULTS: In chordomas, 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 was significantly higher in RP than that in SP group. The numbers of CD163+ TAMs and Foxp3+ Tregs were higher in RP than that in SP group. CONCLUSIONS: Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.
BACKGROUND:Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular endothelial growth factor (VEGF) is a potent activator of angiogenesis that is strongly associated with the tumor-immune microenvironment. These factors have not been elucidated for chordomas. METHODS: 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 following two groups as per the tumor growth rate: patients with slow progression (SP: < 3 mm/year) and those with rapid progression (RP: ≥ 3 mm/year). Thus, the expressions of VEGF-A, VEGFR 1, 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, especially in a comparison between the two groups. RESULTS: In chordomas, 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 was significantly higher in RP than that in SP group. The numbers of CD163+ TAMs and Foxp3+ Tregs were higher in RP than that in SP group. CONCLUSIONS: Expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to tumor growth in patients with chordomas.
Authors: Molly E Heft Neal; Nicole L Michmerhuizen; Kevin J Kovatch; John Henry J Owen; Jingyi Zhai; Hui Jiang; Erin L McKean; Mark E P Prince; J Chad Brenner Journal: J Neurol Surg B Skull Base Date: 2020-10-12
Authors: Franco Rubino; Christopher Alvarez-Breckenridge; Kadir Akdemir; Anthony P Conley; Andrew J Bishop; Wei-Lien Wang; Alexander J Lazar; Laurence D Rhines; Franco DeMonte; Shaan M Raza Journal: Front Oncol Date: 2022-09-29 Impact factor: 5.738