Persistent restoration to the immunosupportive tumor microenvironment in glioblastoma by bevacizumab
Open accessAbstract
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.
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Bevacizumab and other VEGFA signaling suppressors are associated with PD-L1 downregulation by malignant and myeloid cells in preclinical cancer models.
“PD-L1 downregulation by malignant and myeloid cells”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Tamura et al., 2019
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- Authors
- Tamura, R., Tanaka, T., Ohara, K., Miyake, K., Morimoto, Y., Yamamoto, Y., Kanai, R., Akasaki, Y., Murayama, Y., Tamiya, T., Yoshida, K., & Sasaki, H.
- Affiliations
- Keio University (JP)
- Jikei University Kashiwa hospital (JP)
- Kagawa University Hospital (JP)
- Eiju General Hospital (JP)
- The Jikei University Hospital (JP)
- Corresponding author
- Tanaka, Toshihide
- Sasaki, Hikaru
- ORCID
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2018-12-21
- Volume
- 110
- Issue
- 2
- Pages
- 499-508
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC6361613
- OpenAlex
- W2901864445
- Cited by
- 75
- References
- 44
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 17 · 2019: 5 · 2018: 1
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology and the Japan Society for the Promotion of Science (KAKENHI)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- bevacizumab, glioblastoma, tumor microenvironment, immunosuppression, PD-L1, PD-1, tumor-infiltrating T cells, regulatory T cells, Foxp3, tumor-associated macrophages, CD163, vascular endothelial growth factor, recurrent glioblastoma, anti-angiogenic therapy
- MeSH terms
- Bevacizumab, Antineoplastic Agents, Immunological, CD163 Antigen, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Female, Glioblastoma, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Recurrence, Local, Receptors, Cell Surface, Biomarkers, Tumor, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Vascular Endothelial Growth Factor A, Tumor Microenvironment, B7-H1 Antigen
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