Regulatory B cells contribute to the impaired antitumor immunity in ovarian cancer patients

Abstract

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.

Positive and negative functions of B lymphocytes in tumors

“…Increased B-cell subset may lead to poor clinical prognosis in NSCLC. Similar results are also found in ovarian cancer [61]. The population of B10 cells is preferentially enriched in ascites, and their frequency is positively correlated with ovarian cancer severity.…”

“…As a result, Bregs may inhibit T cell proliferation through cell-to-cell contact, thereby leading to anergy or apoptosis [75]. Moreover, B10 cells from the ascites of ovarian tumor [61] can suppress the IFN-γ production of CD8 + T cells. When co-cultured CD8 + T cells with autologous blood B cells or ascitic B cells, the co-cultured group demonstrates significantly decreased IFN-γ production.…”

“…Recently, cytological experiments [62] have indicated that induced by tongue squamous cell carcinoma cells, B cells can convert CD4 + CD25 − T cells into Tregs. In the ascites of ovarian cancer patients, the frequencies of IL-10 + B cells are also positively correlated with the frequencies of CD4 + Foxp3 + Tregs [61]. In another study, when targeting Bregs by Lipoxin A4, the number of Tregs decreases in the draining lymph nodes and tumor tissues [80], thereby emphasizing the important effect of Bregs on inducing the frequency and distribution of Tregs.…”

Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients

“…Within this same study, Zhou et al demonstrated that IL10 + TIL-Bs positively correlated with increased Tregs and decreased survival. B cell–mediated immunoregulation has also been shown using B and T cells isolated from the ascites of ovarian cancer patients (38). However, studies of TIL-Bs from NSCLC patients have not yet been published.…”

The functional role of B cells and their secreted antibodies

“…To date, there is a controversy, since several studies suggest that TIBs are protective [164][165][166] , while others indicate that Bregs are increased in patients with solid tumours, which is associated with increased aggressiveness and inferior patients' outcome [167][168][169][170][171] . In lymphoid malignancies, the anti-tumour immune responses are suppressed by malignant B cells that 'perform' as Bregs via the expression of suppressive ligands [172][173][174] .…”