Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy
| Autor: | Patrick Healy, John H. Sampson, Bryan D. Choi, Gerald E. Archer, Pamela Norberg, James E. Herndon, Robert J. Schmittling, Luis Sanchez-Perez, Elias Sayour, Anirudh Saraswathula, Elizabeth A. Reap, Kendra L. Congdon |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Regulatory B cells Immunology B-cell receptor Lymphocyte Activation Cancer Vaccines Article Antibodies 03 medical and health sciences B-Cell Activating Factor medicine Temozolomide Immunology and Allergy Humans Lymphocyte Count B-cell activating factor Antineoplastic Agents Alkylating B cell B-Lymphocytes Regulatory business.industry Immunotherapy Interleukin-10 Dacarbazine ErbB Receptors Interleukin 10 030104 developmental biology medicine.anatomical_structure Oncology Humoral immunity Vaccines Subunit Peptide vaccine business Glioblastoma |
| Popis: | 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: | OpenAIRE |
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