National Key Laboratory of Protein Engineering and Plant Gene Engineering, Institute of Life Science, Peking University, Beijing, China.
Cytotherapy. 2010 Apr;12(2):190-200. doi: 10.3109/14653240903390803.
Hepatocellular carcinoma (HCC) recurs with high frequency. Characterization of recurrent HCC cells will facilitate the design of future therapeutic strategies for recurrent HCC.
Two cell lines, Hep-11 and Hep-12, were established from the same HCC patient's primary and recurrent tumor tissues, respectively, and then analyzed for stem cell-like properties, immune evasion strategies and immunogenicity.
Compared with Hep-11 cells, Hep-12 cells expressed higher levels of liver progenitor cell makers and displayed persistent tumorigenic potential in the serial transplantation assay. Although Hep-12 cells down-regulated human leukocyte antigen (HLA) class I expression, they could still be recognized and killed by autologous-activated tumor-infiltrating lymphocytes (TIL) in vitro. Pre-treatment with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) increased the expression of HLA class I molecules on Hep-12 cells, and rendered them more susceptible to CD8(+) T-cell-mediated recognition and TIL-mediated cytotoxicity in vitro.
Our results indicate that Hep-12 cells possess stem cell-like properties, are susceptible to autologous-activated TIL-mediated recognition and cytotoxicity, and pre-treatment with TNF-alpha and IFN-gamma enhances their immunogenicity. This is the first evidence to support the hypothesis that immunotherapy can be used to target recurrent HCC cells with stem cell-like properties. This strategy may be an effective therapeutic approach to prevent HCC recurrence and control recurrent HCC growth.
肝细胞癌（HCC）复发率高。对复发性 HCC 细胞的特征进行分析，有助于设计针对复发性 HCC 的未来治疗策略。
从同一 HCC 患者的原发性和复发性肿瘤组织中分别建立了两个细胞系 Hep-11 和 Hep-12，并对其干细胞样特性、免疫逃逸策略和免疫原性进行了分析。
与 Hep-11 细胞相比，Hep-12 细胞表达更高水平的肝祖细胞标志物，并在连续移植实验中表现出持续的致瘤潜能。尽管 Hep-12 细胞下调了人白细胞抗原（HLA）I 类分子的表达，但它们仍能被自体激活的肿瘤浸润淋巴细胞（TIL）在体外识别和杀伤。肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）等细胞因子预处理可增加 Hep-12 细胞 HLA I 类分子的表达，使其更易被 CD8+T 细胞介导的识别和 TIL 介导的细胞毒性在体外。
我们的结果表明，Hep-12 细胞具有干细胞样特性，易受自体激活的 TIL 介导的识别和杀伤，TNF-α和 IFN-γ预处理可增强其免疫原性。这是第一个支持免疫疗法可用于靶向具有干细胞样特性的复发性 HCC 细胞的假说的证据。该策略可能是预防 HCC 复发和控制复发性 HCC 生长的有效治疗方法。
