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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Saraswathula, A; Reap, EA; Choi, BD; Schmittling, RJ; Norberg, PK; Sayour, EJ; Herndon, JE; Healy, P; Congdon, KL; Archer, GE; Sanchez-Perez, L; Sampson, JH

Published Date

  • February 2016

Published In

Volume / Issue

  • 65 / 2

Start / End Page

  • 205 - 211

PubMed ID

  • 26759007

Pubmed Central ID

  • 26759007

Electronic International Standard Serial Number (EISSN)

  • 1432-0851

International Standard Serial Number (ISSN)

  • 0340-7004

Digital Object Identifier (DOI)

  • 10.1007/s00262-015-1784-3

Language

  • eng