Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab

• DOI: 10.1111/cas.13889
• Publication Date: 2018-11-23T09:26:15Z
• Authors: Ryota Tamura; Toshihide Tanaka; Kentaro Ohara; Keisuke Miyake; Yukina Morimoto; Yohei Yamamoto; Ryuichi Kanai; Yasuharu Akasaki; Yuichi Murayama; Takashi Tamiya; Kazunari Yoshida; Hikaru Sasaki
• Keywords: Adult; Aged, 80 and over; Male; Vascular Endothelial Growth Factor A; 0301 basic medicine; Brain Neoplasms; Antigens, Differentiation, Myelomonocytic; Receptors, Cell Surface; Original Articles; Middle Aged; Immunohistochemistry; B7-H1 Antigen; 3. Good health; Bevacizumab; 03 medical and health sciences; Antineoplastic Agents, Immunological; Antigens, CD; Biomarkers, Tumor; Tumor Microenvironment; Humans; Female; Neoplasm Recurrence, Local; Glioblastoma; Aged

Although vascular endothelial growth factor (VEGF) promotes the immunosuppressive microenvironment, the efficacy of bevacizumab (Bev) on tumor immunity has not been fully investigated. The present study used 47 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naïve Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory Bev group). The paired samples of the initial and post‐Bev recurrent tumors from 9 patients were included. The expression of programmed cell death‐1 (PD‐1)/PD ligand‐1 (PD‐L1), CD3, CD8, Foxp3, and CD163 was analyzed by immunohistochemistry. The PD‐L1+ tumor cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The PD‐1+ cells significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (P < .01 for each). The amount of CD3+ and CD8+ T cell infiltration increased in the refractory Bev group compared with the naïve Bev group (CD3, P < .01; CD8, P = .06). Both Foxp3+ regulatory T cells and CD163+ tumor‐associated macrophages significantly decreased in the effective or refractory Bev group compared with the naïve Bev group (Foxp3, P < .01 for each; CD163, P < .01 for each). These findings were largely confirmed by comparing paired initial and post‐Bev recurrent tumors. Bevacizumab restores the immunosupportive tumor microenvironment in glioblastomas, and this effect persists during long‐term Bev therapy.