Regulatory B1a Cells Suppress Melanoma Tumor Immunity via IL-10 Production and Inhibiting T Helper Type 1 Cytokine Production in Tumor-Infiltrating CD8+ T Cells

Abstract

In tumor immunity, the participation of IL-10eproducing regulatory B cells (Bregs), which play an important role in suppressing immune responses, is unclear. In this study, we demonstrated an increase in B16F10 melanoma growth and a decrease in the proportion of IFN-ge and TNF-aesecreting tumor-infiltrating CD8 þ T cells in B cellespecific PTEN-deficient mice in which Bregs were expanded. The number of tumor-infiltrating Bregs significantly increased in B cellespecific PTEN-deficient mice. More than 50% of tumor-infiltrating B cells consisted of Bregs, predominantly CD19 þ CD5 þ CD43 þ B1a Bregs, in both B cellespecific PTEN-deficient and control mice. Adoptive B1a B cell transfer, which includes >30% of Bregs, increased melanoma growth, whereas non-B1a B cell transfer, which includes <2% of Bregs, exhibited no effect. In addition, adoptive transfer of B1a B cells from wild-type mice, but not IL-10 e/e mice, exacerbated B16F10 melanoma growth. The current study indicates that B1a Bregs negatively regulate anti-melanoma immunity by producing IL-10 and reducing T helper 1 type cytokine production in tumor-infiltrating CD8 þ T cells. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.

Elevated serum B‐cell activating factor levels in patients with dermatomyositis: Association with interstitial lung disease

“…B cells are divided into two opposing B‐cell subsets, namely regulatory B cells and effector B cells . Regulatory B cells negatively regulate immune responses by the production of anti‐inflammatory cytokines, such as interleukin (IL)‐10 . Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases .…”

“…18 Regulatory B cells negatively regulate immune responses by the production of anti-inflammatory cytokines, such as interleukin (IL)-10. 19,20 Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. [21][22][23] cytokines, such as IL-6.…”

Cells to Surgery Quiz: October 2019

“…IL-10 inhibitors are a known negative regulator of autoimmunity and inflammation (Bouaziz et al, 2008;Iwata et al, 2011;Matsushita et al, 2008). Kobayashi et al (2019) showed that in Bregs where PTEN was inactivated, there was a significant increase in B16F10 volume and decreased survival in PTEN-deficient mice injected subcutaneously with B16F10 melanoma cells compared with control mice (Kobayashi et al, 2019). See Figure 1 from Kobayashi et al (2019).…”

“…2. What likely effect would increased PTEN have on B16F10 melanoma volume and mortality as described in Kobayashi et al (2019)?…”

“…3. As described in Kobayashi et al (2019) Melanoma is the deadliest cutaneous cancer (Siegel et al, 2019), and its incidence continues to rise. Melanomas are typically diagnosed through visual examination, with the goal being early detection.…”