Chen Xiaokun, Liu Xiao, Du Shunda
Department of Liver Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Cancers (Basel). 2023 Oct 19;15(20):5046. doi: 10.3390/cancers15205046.
Hepatocellular carcinoma (HCC) is a rapidly rising global health concern, ranking as the third-leading cause of cancer-related mortality. Despite medical advancements, the five-year survival rate remains a dismal 18%, with a daunting 70% recurrence rate within a five-year period. Current systematic treatments, including first-line sorafenib, yield an overall response rate (ORR) below 10%. In contrast, immunotherapies have shown promise by improving ORR to approximately 30%. The IMbravel150 clinical trial demonstrates that combining atezolizumab and bevacizumab surpasses sorafenib in terms of median progression-free survival (PFS) and overall survival (OS). However, the therapeutic efficacy for HCC patients remains unsatisfactory, highlighting the urgent need for a comprehensive understanding of antitumor responses and immune evasion mechanisms in HCC. In this context, understanding the immune landscape of HCC is of paramount importance. Tumor-infiltrating T cells, including cytotoxic T cells, regulatory T cells, and natural killer T cells, are key components in the antitumor immune response. This review aims to shed light on their intricate interactions within the immunosuppressive tumor microenvironment and explores potential strategies for revitalizing dysfunctional T cells. Additionally, current immune checkpoint inhibitor (ICI)-based trials, ICI-based combination therapies, and CAR-T- or TCR-T-cell therapies for HCC are summarized, which might further improve OS and transform the management of HCC in the future.
肝细胞癌（HCC）是一个日益引起全球关注的健康问题，是癌症相关死亡的第三大原因。尽管医学取得了进步，但其五年生存率仍低至18%，五年内复发率高达70%，令人望而生畏。目前的系统治疗方法，包括一线药物索拉非尼，总体缓解率（ORR）低于10%。相比之下，免疫疗法已显示出前景，将ORR提高到了约30%。IMbravel150临床试验表明，阿替利珠单抗和贝伐单抗联合使用在中位无进展生存期（PFS）和总生存期（OS）方面优于索拉非尼。然而，对HCC患者的治疗效果仍不尽人意，这突出表明迫切需要全面了解HCC中的抗肿瘤反应和免疫逃逸机制。在此背景下，了解HCC的免疫格局至关重要。肿瘤浸润性T细胞，包括细胞毒性T细胞、调节性T细胞和自然杀伤T细胞，是抗肿瘤免疫反应的关键组成部分。本综述旨在阐明它们在免疫抑制性肿瘤微环境中的复杂相互作用，并探索恢复功能失调T细胞的潜在策略。此外，还总结了目前基于免疫检查点抑制剂（ICI）的试验、基于ICI的联合疗法以及用于HCC的CAR-T或TCR-T细胞疗法，这些疗法可能会进一步改善总生存期，并在未来改变HCC的治疗方式。
