Immune modulation associated with vascular endothelial growth factor (VEGF) blockade in patients with glioblastoma
| Autor: | Brock C. Christensen, Alissa A. Thomas, Arti B. Gaur, Marc S. Ernstoff, Gilbert J. Rahme, Camilo E. Fadul, Sandra E. Steel, Chery A. Whipple, Melissa C. Davis, Thomas H. Hampton, Jan L. Fisher, Lionel D. Lewis, Gregory J. Tsongalis |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Placental growth factor Cancer Research medicine.medical_treatment Immunology T-Lymphocytes Regulatory Peripheral blood mononuclear cell Disease-Free Survival 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Temozolomide medicine Humans Immunology and Allergy Aged Tumor microenvironment Brain Neoplasms business.industry Growth factor Chemoradiotherapy Immunotherapy Middle Aged Bevacizumab Dacarbazine Vascular endothelial growth factor 030104 developmental biology Cytokine Oncology chemistry 030220 oncology & carcinogenesis Leukocytes Mononuclear Cytokines Female Glioblastoma business medicine.drug |
| Zdroj: | Cancer Immunology, Immunotherapy. 66:379-389 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-016-1941-3 |
| Popis: | Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV). Eleven patients with newly diagnosed glioblastoma were treated with radiation, TMZ, and BEV, following surgery. We measured immune-related PBMC subsets using multi-parameter flow cytometry and plasma cytokine and growth factor concentrations using electrochemiluminescence-based multiplex analysis at baseline and after 6 weeks of treatment. The absolute number of peripheral blood regulatory T cells (Tregs) decreased significantly following treatment. The lower number of peripheral Tregs was associated with a CD4+ lymphopenia, and thus, the ratio of Tregs to PBMCs was unchanged. The addition of bevacizumab to standard radiation and temozolomide led to the decrease in the number of circulating Tregs when compared with our prior study. There was a significant decrease in CD8+ cytotoxic and CD4+ recent thymic emigrant T cells, but no change in the number of myeloid-derived suppressor cells. Significant increases in plasma VEGF and placental growth factor (PlGF) concentrations were observed. Treatment with radiation, TMZ, and BEV decreased the number but not the proportion of peripheral Tregs and increased the concentration of circulating VEGF. This shift in the peripheral immune cell profile may modulate the tumor environment and have implications for combining immunotherapy with anti-angiogenic therapy. |
| Databáze: | OpenAIRE |
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