Cancer Immunoregulation Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy.
Cancer Immunoregulation Unit, Istituto Nazionale Tumori - IRCCS - "Fond G. Pascale", Naples, Italy.
Ann Hepatol. 2019 Mar-Apr;18(2):291-297. doi: 10.1016/j.aohep.2019.04.003. Epub 2019 Apr 25.
Hepatocellular carcinoma (HCC) is considered an immunogenic tumor that arises in chronically inflamed livers due to underlying chronic liver disease caused by viral and non-viral pathogenesis. This inflammation leads to tumor development and is associated to higher tumor immunogenicity. For this reason immunotherapeutic approaches may be suitable therapeutic strategies for HCC. Indeed, several preclinical and clinical data support this hypothesis showing that immunotherapy and even more their combination may be a good alternative candidate for the treatment of HCC patients. However, considering that the liver plays a central role in host defense as well as in the maintenance of self-tolerance, it is characterized by a strong intrinsic immune suppressive microenvironment as well as by a high immune evasion, which may represent a major impediment for an effective immune response against tumor. Furthermore, the low expression of tumor antigens on liver cancer cells leads to a lower T-cell activation and tumor infiltration, resulting in a less efficient control of the tumor growth and, consequently, in a worse clinical outcome. For this reason, strategies should be developed to counteract the different factors in the HCC tumor microenvironment playing a major role in reducing the effects of immunotherapy.
肝细胞癌 (HCC) 被认为是一种免疫原性肿瘤，它发生在慢性炎症的肝脏中，是由病毒和非病毒发病机制引起的潜在慢性肝病引起的。这种炎症导致肿瘤的发展，并与更高的肿瘤免疫原性相关。因此，免疫治疗方法可能是 HCC 的一种合适的治疗策略。事实上，一些临床前和临床数据支持这一假设，表明免疫疗法，甚至更多的联合免疫疗法，可能是治疗 HCC 患者的一个很好的候选方案。然而，由于肝脏在宿主防御以及自身耐受的维持中起着核心作用，它具有强烈的内在免疫抑制微环境和高度的免疫逃逸，这可能是对肿瘤产生有效免疫反应的主要障碍。此外，肝癌细胞上肿瘤抗原的低表达导致 T 细胞的激活和肿瘤浸润减少，从而导致肿瘤生长的控制效果降低，进而导致更差的临床结果。因此，应该制定策略来对抗 HCC 肿瘤微环境中的不同因素，这些因素在降低免疫疗法的效果方面起着重要作用。
