The five-year survival rate of melanoma worsens significantly with advancing tumor stage. We hypothesized that regulatory B cells (Breg) might have participated in the pathogenesis of melanoma. In this study, the PD-L1+ Breg cells were investigated. The expression of PD-L1 by circulating B cells was very low in healthy controls. In melanoma patients, on the other hand, the expression of PD-L1 by circulating B cells was significantly elevated in a manner that was positively associated with tumor stage, with the highest level in stage IV bone metastasis patients. Compared to total B cells, PD-L1+ B cells presented higher IgM and higher IgD expression, and were almost exclusively CD20+CD27-, suggesting that the PD-L1+ B cells exhibited a naive B cell-like phenotype. Healthy naive B cells, which presented little PD-L1, and stage I and stage II melanoma patient naive B cells, which presented detectable but low PD-L1, were unable to suppress T cell response. However, stage III and stage IV naive B cells, which presented moderate PD-L1, could significantly suppress T cell response in a PD-L1-dependent manner. We further found that the level of PD-L1+ B cells was significantly higher in bone metastasis than in the primary tumors. Overall, we demonstrated that PD-L1+ B cells were upregulated in advanced melanoma and were enriched in metastasis compared to primary tumors. Furthermore, PD-L1+ naive B cells could act as a T cell suppressor in a PD-L1-dependent manner.

中文翻译：

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在患有骨转移的黑色素瘤患者中，PD-L1 +调节性B细胞以PD-L1依赖性方式充当T细胞抑制剂。

黑色素瘤的五年生存率随着肿瘤阶段的发展而显着恶化。我们假设调节性B细胞（Breg）可能参与了黑色素瘤的发病机理。在这项研究中，研究了PD-L1 + Breg细胞。在健康对照组中，循环B细胞的PD-L1表达非常低。另一方面，在黑色素瘤患者中，循环B细胞的PD-L1表达以与肿瘤分期呈正相关的方式显着升高，在IV期骨转移患者中水平最高。与总的B细胞相比，PD-L1 + B细胞表现出更高的IgM和更高的IgD表达，并且几乎都是CD20 + CD27-，这表明PD-L1 + B细胞表现出了幼稚的B细胞样表型。健康的幼稚B细胞，几乎没有PD-L1，I期和II期黑色素瘤患者的初次B细胞表现出可检测到的PD-L1低，但不能抑制T细胞反应。但是，呈现中度PD-L1的III期和IV期幼稚B细胞可以以PD-L1依赖性方式显着抑制T细胞反应。我们进一步发现，在骨转移中，PD-L1 + B细胞的水平明显高于原发性肿瘤。总体而言，我们证明，与原发性肿瘤相比，PD-L1 + B细胞在晚期黑色素瘤中表达上调，并且在转移中富集。此外，PD-L1 +幼稚B细胞可以以PD-L1依赖的方式充当T细胞抑制剂。可以以PD-L1依赖性方式显着抑制T细胞反应。我们进一步发现，在骨转移中，PD-L1 + B细胞的水平明显高于原发性肿瘤。总体而言，我们证明，与原发性肿瘤相比，PD-L1 + B细胞在晚期黑色素瘤中表达上调，并且在转移中富集。此外，PD-L1 +幼稚B细胞可以以PD-L1依赖的方式充当T细胞抑制剂。可以以PD-L1依赖性方式显着抑制T细胞反应。我们进一步发现，在骨转移中，PD-L1 + B细胞的水平明显高于原发性肿瘤。总体而言，我们证明，与原发性肿瘤相比，PD-L1 + B细胞在晚期黑色素瘤中表达上调，并且在转移中富集。此外，PD-L1 +幼稚B细胞可以以PD-L1依赖的方式充当T细胞抑制剂。