PDF(Pubmed)
Abstract：
Hepatocellular carcinoma (HCC), one of the leading causes of cancer‑related mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multi‑tyrosine kinase inhibitors approved for first‑line therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of non‑apoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune \'cold\' tumors into immune \'hot\' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.
摘要：
肝细胞癌（HCC），全球癌症相关死亡率的主要原因之一，在早期阶段很难识别，并且容易转移，这种疾病的患者预后较差。肝癌的治疗选择有限，即使是激进的治疗也会在短期内复发或转化的风险。此外，批准用于一线治疗的多酪氨酸激酶抑制剂有明显的缺点，包括耐药性和副作用。免疫检查点抑制剂（ICI）的兴起和突破为HCC免疫治疗提供了新的方向，但这些都有低反应率的缺点。由于避免细胞凋亡是癌症的普遍特征，诱导非凋亡性调节性细胞死亡(NARCD)是HCC免疫治疗的新策略.目前,NARCD路径，包括铁性凋亡,焦亡和坏死，是免疫原性细胞死亡的新的潜在形式，它们与抗肿瘤免疫有协同作用，将免疫“冷”肿瘤转化为免疫“热”肿瘤并发挥抗肿瘤作用。因此,这些途径可能作为HCC的一种新的治疗策略。在本次审查中，铁死亡的作用，讨论了HCC抗肿瘤免疫中的焦亡和坏死，以及相关的靶标和信号通路，并总结了ICIs联合治疗的现状。靶向铁凋亡的前景，还考虑了HCC免疫治疗中的焦亡和坏死。
