Digestive Diseases Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province 130041, People's Republic of China.
Digestive Diseases Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin Province 130041, People's Republic of China.
Int Immunopharmacol. 2021 Nov;100:108161. doi: 10.1016/j.intimp.2021.108161. Epub 2021 Sep 20.
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 CD3CD19CD56NKp46 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) 细胞是新近鉴定的淋巴细胞亚群，通过分泌白细胞介素-18 (IL-18) 在传染病中呈现免疫调节特性。然而，NKB 细胞功能及其在肝细胞癌 (HCC) 中的调节作用尚不清楚。本研究纳入了 72 例 HCC 患者和 25 名对照者。采用流式细胞术检测外周血和肝浸润 CD3CD19CD56NKp46 细胞。采用 ELISA 法检测血清 IL-35 和 NKB 细胞分泌细胞因子水平。在 CD8 T 细胞和 HepG2 细胞直接共培养系统中评估 IL-35 对外周血和肝浸润 NKB 细胞的调节活性。与对照组相比，HCC 患者外周血 NKB 细胞和 IL-18 分泌减少，而 HCC 肿瘤部位肝浸润 NKB 细胞和 IL-18 分泌也减少。升高的 IL-35 水平与 HCC 患者 NKB 细胞百分比和 IL-18 产生呈负相关。NKB 细胞诱导 CD8 T 细胞细胞毒性升高，而这种增强可被 IL-18 结合蛋白抑制。IL-35 刺激可降低 NKB 细胞百分比和 IL-18 产生，从而抑制 HCC 患者 NKB 细胞介导的 CD8 T 细胞细胞毒性。我们的研究数据表明，IL-35 可能抑制 HCC 患者的 NKB 细胞活性。
