Emerging immunotherapy for HCC: A guide for hepatologists.
Emerging immunotherapy for HCC: A guide for hepatologists.
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DOI：
10.1002/hep.32447
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发表时间：
2022-06
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--
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肝细胞癌（HCC）是全球最常见的癌症之一，也是全球癌症相关死亡的第三大原因。HCC占所有原发性肝癌病例的近90%。大约一半的HCC患者在其疾病过程中接受全身治疗，特别是在疾病的晚期。免疫肿瘤学已经改变了人类癌症治疗的范式，在包括HCC在内的各种恶性肿瘤的患者亚组中具有强大而持久的抗肿瘤活性。atezolizumab和贝伐单抗（一种抗血管内皮生长因子中和抗体）的免疫检查点抑制已成为晚期HCC患者的一线治疗。除了免疫检查点抑制之外，目前正在研究诸如溶瘤病毒免疫疗法和过继性T细胞转移的免疫治疗策略。HCC的肿瘤免疫微环境具有显著的免疫抑制因素，可能影响对免疫治疗的反应。主要的未解决的挑战包括定义免疫治疗在HCC早期阶段的作用，评估采用免疫微环境靶向加上免疫检查点抑制的组合策略，以及确定对目前可用的免疫疗法无反应的患者的治疗策略。在此，我们回顾了免疫疗法治疗肝癌的原理、机制基础和支持性临床前证据，以及现有的临床证据，以及正在进行的免疫疗法临床试验。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the third leading cause of cancer-related death globally. HCC comprises nearly 90% of all cases of primary liver cancer. Approximately half of all HCC patients receive systemic therapy during their disease course, particularly in the advanced stages of disease. Immuno-oncology has been paradigm shifting for the treatment of human cancers, with strong and durable anti-tumor activity in a subset of patients across a variety of malignancies including HCC. Immune checkpoint inhibition with atezolizumab and bevacizumab, an anti-vascular endothelial growth factor neutralizing antibody, has become first line therapy for patients with advanced HCC. Beyond immune checkpoint inhibition, immunotherapeutic strategies such as oncolytic viroimmunotherapy and adoptive T cell transfer are currently under investigation. The tumor immune microenvironment of HCC has significant immunosuppressive elements that may impact response to immunotherapy. Major unmet challenges include defining the role of immunotherapy in earlier stages of HCC, evaluating combinatorial strategies that employ targeting of the immune microenvironment plus immune checkpoint inhibition, and identifying treatment strategies for patients who do not respond to the currently available immunotherapies. Herein, we review the rationale, mechanistic basis and supporting preclinical evidence, and available clinical evidence for immunotherapies in HCC as well as ongoing clinical trials of immunotherapy.
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