Regulatory B cells contribute to the impaired antitumor immunity in ovarian cancer patients
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Multiple factors in the tumor microenvironment were found to inhibit antitumor adaptive immune responses, allowing tumor persistence and growth. In this study, ascites from ovarian cancer patients were collected. We observed that a population of interleukin-10+ B (IL-10+ B) cells was preferentially enriched in the ascites. This population was associated with naive B cell phenotype or IgM or class-switched memory B cell phenotypes. The frequencies of IL-10+ B cells were negatively correlated with the frequencies of interferon gamma-producing (IFN-g+) CD8+ T cells and were positively correlated with the frequencies of Foxp3+ CD4+ T cells. To examine whether increased IL-10+ B cells in ascites could directly result in increased suppression of IFN-g production by CD8+ T cells, we cocultured CD8+ T cells with autologous blood B cells or ascitic B cells and found that CD8+ T cells cocultured with ascitic B cells demonstrated significantly suppressed IFN-g production. This suppression was in part mediated by IL-10 as well as low CD80/CD86 expression, since depletion of IL-10 and stimulation of CD28 partially reverted IL-10+ B cell-mediated suppression. Together, these data demonstrated an additional regulatory mechanism in the tumor microenvironment, which utilizes IL-10+ B cells.
KeywordsB cell Ovarian cancer
This work was supported by Shandong Provincial Medical and Health Science Technology Development Project (2014WS0011) and Jinan Science Technology Development Project (2014–34).
Conflicts of interest
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