Schmidt Nathalie, Thimme Robert
Department of Medicine II, University of Freiburg, Freiburg, Germany.
Dig Dis. 2016;34(4):429-37. doi: 10.1159/000444558. Epub 2016 May 11.
Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide with a high mortality. The available treatment options are limited, thus the development of new therapeutic approaches is of a high clinical significance.
The immune system plays a central role in the pathogenesis of HCC by supporting tumor growth, tumor survival, angiogenesis and the development of vascular infiltration and metastasis. In contrast, the immune system also exhibits a protective role in tumor surveillance, and specific CD8+ T-cells can be detected for various tumor-associated antigens. However, antitumoral potential of the immune system is limited by various inhibitory mechanisms, for example, an impaired priming and activation of CD8+ T-cells, inhibitory cells (e.g., regulatory T-cells) or the expression of inhibitory receptors (e.g., programmed cell death-1 and cytotoxic T-lymphocyte antigen-4). Immunotherapeutic strategies addressing these inhibitory mechanisms, for example, by providing a source of tumor antigens, depleting immunosuppressive cells or blocking inhibitory receptors, aim to induce and boost naturally occurring antitumoral immune responses.
HCC is a tumor with a high incidence and mortality in developing countries as well as in the Western world. Due to the immune system's central role in the pathogenesis and surveillance of HCC, immunotherapy is a new treatment option that has yielded first promising results.
肝细胞癌(HCC)是全球第六大常见恶性肿瘤,死亡率很高。现有的治疗选择有限,因此开发新的治疗方法具有很高的临床意义。
免疫系统在HCC的发病机制中起着核心作用,它支持肿瘤生长、肿瘤存活、血管生成以及血管浸润和转移的发展。相反,免疫系统在肿瘤监测中也发挥着保护作用,并且可以检测到针对各种肿瘤相关抗原的特异性CD8 + T细胞。然而,免疫系统的抗肿瘤潜力受到多种抑制机制的限制,例如,CD8 + T细胞的启动和激活受损、抑制性细胞(如调节性T细胞)或抑制性受体的表达(如程序性细胞死亡-1和细胞毒性T淋巴细胞抗原-4)。针对这些抑制机制的免疫治疗策略,例如通过提供肿瘤抗原来源、清除免疫抑制细胞或阻断抑制性受体,旨在诱导和增强自然发生的抗肿瘤免疫反应。
HCC在发展中国家以及西方世界都是一种发病率和死亡率很高的肿瘤。由于免疫系统在HCC的发病机制和监测中起着核心作用,免疫疗法是一种新的治疗选择,已经取得了初步的 promising 结果。 (注:原文中“promising”拼写错误,正确拼写应为“promising”,这里按正确意思翻译为“有前景的”)