Antitumor responses are enhanced by B-cell depletion via decrease in IL-10 production

B-cell depletion may enhance antitumor immune responses by decreasing IL-10 production from B cells.

  According to recent research from the United States, “B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells in the development of antitumor immunity using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse melanoma, or MCA304 mouse sarcoma cells.”

  “To screen tumors for susceptibility to B-cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in vitro,” said Satoshi Inoue and colleagues at the U.S. Food and Drug Administration and U.S. National Institutes of Health.

“When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors), IFN-gamma production from CD8 T cells and natural killer cells was markedly decreased in WT compared with BKO cultures,” the researchers reported. “IFN-gamma production was correlated with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL-10) production by B cells.”

  “Sorted WT B cells produced more IL-10 than CD40 knockout (CD40KO) B cells when co-cultured with EL-4 gag or D5 (but not MCA304),” the scientists noted. “IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT B cells (partially by CD40KO B cells) or recombinant mouse IL-10.”

  “In vivo tumor progression mirrored in vitro studies in that WT mice were unable to control tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in BKO mice,” they continued. “Robust in vivo antitumor CTLs developed only in BKO tumor-challenged mice.”

  “Our studies provide the first mechanistic basis for the concept that B-cell depletion could therapeutically enhance antitumor immune responses to certain tumors by decreasing IL-10 production from B cells,” stated the authors.

  Inoue and associates published their study in Cancer Research (Inhibitory effects of B cells on antitumor immunity. Cancer Res, 2006;66(15):7741-7747).

  For additional information, contact Dorothy Scott, Center for Biologics Evaluation and Research, Division of Hematology, Food and Drug Administration, 1401 Rockville Pike, HFM-345, Rockville, MD 20852-1448, USA. E-mail: .(JavaScript must be enabled to view this email address).