Natural killer-like B (NKB) cells are newly identified lymphocyte subset, which present immunomodulatory property in infectious diseases through secretion of interleukin-18 (IL-18). However, the role of NKB cells function and its regulation in hepatocellular carcinoma (HCC) is not elucidated. Seventy-two HCC patients and twenty-five controls were enrolled. Peripheral and liver-infiltrating CD3^-CD19⁺CD56⁺NKp46⁺ cells were investigated by flow cytometry. Serum IL-35 and NKB cell-secreting cytokine level was measured by ELISA. The regulatory activity of IL-35 to peripheral and liver-infiltrating NKB cells was assessed in direct co-culture system between CD8⁺ T cells and HepG2 cells. Peripheral NKB cells and IL-18 secretion were reduced in HCC patients, while liver-infiltrating NKB cells and IL-18 secretion were also decreased in HCC tumor sites. Increased IL-35 level was negatively correlated with NKB cell percentage and IL-18 production in HCC. NKB cells induced the elevation of CD8⁺ T cell cytotoxicty, and this enhancement could be inhibited by IL-18 binding protein. IL-35 stimulation dampened NKB cell percentage and IL-18 production, leading to the suppression of NKB cell-mediated CD8⁺ T cell cytotoxicity in HCC patients. Our current data revealed that IL-35 might suppress NKB cell activity in HCC patients.

自然杀伤样 B (NKB) 细胞是新发现的淋巴细胞亚群，通过分泌白细胞介素 18 (IL-18) 在传染病中具有免疫调节特性。然而，NKB 细胞功能及其在肝细胞癌 (HCC) 中的调节作用尚未阐明。招募了 72 名 HCC 患者和 25 名对照。通过流式细胞术研究外周和肝脏浸润性 CD3 ^- CD19 ⁺ CD56 ⁺ NKp46 ^+细胞。通过ELISA测量血清IL-35和NKB细胞分泌细胞因子水平。^{在 CD8 +}之间的直接共培养系统中评估了 IL-35 对外周和肝浸润 NKB 细胞的调节活性T 细胞和 HepG2 细胞。HCC患者的外周NKB细胞和IL-18分泌减少，而HCC肿瘤部位的肝脏浸润NKB细胞和IL-18分泌也减少。IL-35 水平升高与 HCC 中的 NKB 细胞百分比和 IL-18 产生呈负相关。NKB 细胞诱导 CD8 ⁺ T 细胞细胞毒性的升高，这种增强可被 IL-18 结合蛋白抑制。IL-35 刺激抑制了 NKB 细胞百分比和 IL-18 的产生，从而抑制了 HCC 患者中 NKB 细胞介导的 CD8 ⁺ T 细胞细胞毒性。我们目前的数据显示，IL-35 可能会抑制 HCC 患者的 NKB 细胞活性。