Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China; Department of General Surgery, Heyuan People's Hospital, Heyuan 517001, China.
Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China; Department of Central Laboratory, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, PR China.
Biochem Biophys Res Commun. 2021 Jan 8;535:80-86. doi: 10.1016/j.bbrc.2020.11.118. Epub 2020 Dec 18.
Hepatocellular carcinoma (HCC) remains a public health challenge that requires dedication to develop new treatment options due to its high recurrence rate and poor prognosis. Interferon-producing killer dendritic cell (IKDC) is a subset of INF-γ secreting immune cells that modulates acquired immunity and possesses cytolytic ability. We modified IKDC isolated from the murine spleen with T-bet lentiviral transduction to enhance its cytotoxicity against HCC, and acquired IKDC overexpressing T-bet (T-bet-IKDC) for the first time. T-bet-IKDC has increased INF-γ secretion and surface expression of NKG2D and TRAIL. In vitro study by MTS assay and flow cytometry showed enhanced anti-tumor effect against H22 cells via apoptosis induction in a dose- and time-dependent manner. In vivo study on H22-bearing mice confirmed increased INF-γ secretion, reduced tumor size, increased caspase 3 cleavage, and up-regulation of cytotoxic molecules after T-bet-IKDC administration. The study suggested prospective application of T-bet-IKDC in future immunotherapy for HCC treatment.
肝细胞癌 (HCC) 仍然是一个公共卫生挑战，由于其高复发率和预后不良，需要致力于开发新的治疗方案。产生干扰素的杀伤性树突状细胞 (IKDC) 是 INF-γ 分泌免疫细胞的一个亚群，调节获得性免疫并具有细胞溶解能力。我们通过 T-bet 慢病毒转导修饰了从鼠脾脏中分离出的 IKDC，以增强其对 HCC 的细胞毒性，并首次获得了过表达 T-bet 的 IKDC（T-bet-IKDC）。T-bet-IKDC 增加了 INF-γ 的分泌和 NKG2D 和 TRAIL 的表面表达。MTS 测定和流式细胞术的体外研究表明，通过诱导细胞凋亡，T-bet-IKDC 以剂量和时间依赖的方式增强了对 H22 细胞的抗肿瘤作用。在 H22 荷瘤小鼠的体内研究中证实，T-bet-IKDC 给药后增加了 INF-γ 的分泌，减少了肿瘤大小，增加了半胱天冬酶 3 的切割，并上调了细胞毒性分子。该研究表明 T-bet-IKDC 有希望应用于未来 HCC 的免疫治疗。
