Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China.
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, China.
Cytokine. 2019 Jun;118:115-123. doi: 10.1016/j.cyto.2018.04.003. Epub 2018 Apr 11.
Interleukin (IL)-7 stimulation improves virus- and tumor-specific CD8 T cell responses. However, the role of IL-7 in modulation of dysfunctional CD8 T cells in hepatocellular carcinoma (HCC) was not completely understood. In this study, a total of 37 HLA-A2 restricted patients with HCC and 16 healthy individuals were enrolled. IL-7 expression and its receptor α chain CD127 level was measured. The regulatory activity of IL-7 to peripheral and liver-resident CD8 T cells was investigated in co-culture systems which were directly or indirectly contacted with HCC cell line HepG2 in vitro. Serum IL-7 concentration was significantly reduced in HCC patients, while effective anti-tumor treatment up-regulated IL-7 expression. However, CD127 expression was comparable on peripheral CD8 T cells from either HCC patients and healthy individuals, and was also similar on liver-resident CD8 T cells from either normal tissues and HCC specimens. CD8 T cells purified from normal liver tissues also presented stronger cytotoxicity compared with those from HCC specimens prior to and post IL-7 treatment. Moreover, IL-7 stimulation not only augmented cytotoxicity of peripheral and liver-resident CD8 T cells, but also promoted IFN-γ and TNF-α production by CD8 T cells in direct contact co-culture system. This process was accompanied by down-regulation of programmed death-1 (PD-1) expression on CD8 T cells. Our present data indicated that IL-7 enhanced both cytolytic and noncytolytic activity of CD8 T cells to HCC probably via repression of PD-1 under direct tumor cells presentation. IL-7 might be considered as one of the therapeutic candidates for HCC treatment.
白细胞介素 (IL)-7 刺激可改善病毒和肿瘤特异性 CD8 T 细胞应答。然而，IL-7 在调节肝细胞癌 (HCC) 中功能失调的 CD8 T 细胞中的作用尚未完全阐明。在这项研究中，共纳入了 37 名 HLA-A2 受限的 HCC 患者和 16 名健康个体。测量了 IL-7 表达及其受体α链 CD127 水平。在体外直接或间接接触 HCC 细胞系 HepG2 的共培养系统中，研究了 IL-7 对周围和肝驻留 CD8 T 细胞的调节活性。HCC 患者的血清 IL-7 浓度显著降低，而有效的抗肿瘤治疗可上调 IL-7 表达。然而，外周血 CD8 T 细胞上的 CD127 表达在 HCC 患者和健康个体之间无差异，肝驻留 CD8 T 细胞上的 CD127 表达在正常组织和 HCC 标本之间也无差异。与 HCC 标本相比，正常肝组织中分离的 CD8 T 细胞在接受 IL-7 治疗前后均具有更强的细胞毒性。此外，IL-7 刺激不仅增强了外周血和肝驻留 CD8 T 细胞的细胞毒性，而且还促进了直接接触共培养系统中 CD8 T 细胞 IFN-γ和 TNF-α的产生。这一过程伴随着 CD8 T 细胞上程序性死亡受体-1（PD-1）表达的下调。我们的研究数据表明，IL-7 通过在直接肿瘤细胞呈递下抑制 PD-1，增强了 CD8 T 细胞对 HCC 的细胞毒性和非细胞毒性活性。IL-7 可能被视为 HCC 治疗的候选治疗药物之一。
