Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

Autor: Saraswathula A; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA., Reap EA; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Choi BD; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC, USA., Schmittling RJ; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Norberg PK; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Sayour EJ; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC, USA., Herndon JE 2nd; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA., Healy P; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA., Congdon KL; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Archer GE; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Sanchez-Perez L; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA., Sampson JH; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu.; Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery, Duke University Medical Center, Box 3050, Durham, NC, 27710, USA. john.sampson@duke.edu.; Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu.; Department of Pathology, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2016 Feb; Vol. 65 (2), pp. 205-11. Date of Electronic Publication: 2016 Jan 12.
DOI: 10.1007/s00262-015-1784-3
Abstrakt: Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.
Databáze: MEDLINE
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