为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.
Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.
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肝细胞癌(HCC)是全球最致命的癌症之一,复发率高。70-80%的患者出现症状延迟,导致诊断时已处于晚期,通常与慢性肝病相关。程序性细胞死亡蛋白1(PD-1)阻断疗法最近已成为包括HCC在内的多种晚期恶性肿瘤临床管理中有前景的治疗选择,这是由于耗竭的TIL(肿瘤浸润淋巴细胞)被激活以及T细胞功能改善的结果。
然而,许多HCC患者对PD-1阻断疗法无应答,且免疫相关不良事件(irAEs)的多样性限制了其临床应用。因此,许多有效的联合策略正在发展,包括与抗PD-1抗体联合以及其他从化疗到靶向治疗的治疗方法,以改善晚期HCC患者的治疗结果并激发协同抗肿瘤效应。不幸的是,联合治疗可能比单药治疗有更多副作用。尽管如此,识别合适的预测性生物标志物可以通过区分对PD-1抑制剂单药或联合策略应答最佳的患者,有助于管理潜在的免疫相关不良事件。在本综述中,我们总结了PD-1阻断疗法对晚期HCC患者的治疗潜力。
此外,将简要介绍影响患者对抗PD-1抗体应答的关键预测性生物标志物。
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world, with a high relapse rate. Delayed symptom onset observed in 70-80% of patients leads to diagnosis in advanced stages commonly associated with chronic liver disease. Programmed cell death protein 1 (PD-1) blockade therapy has recently emerged as a promising therapeutic option in the clinical management of several advanced malignancies, including HCC, due to the activation of exhausted tumor-infiltrating lymphocytes and improved outcomes of T-cell function.
However, many people with HCC do not respond to PD-1 blockade therapy, and the diversity of immune-related adverse events (irAEs) restricts their clinical utility.
Therefore, numerous effective combinatory strategies, including combinations with anti-PD-1 antibodies and other therapeutic methods ranging from chemotherapy to targeted therapies, are evolving to improve therapeutic outcomes and evoke synergistic anti-tumor impressions in patients with advanced HCC. Unfortunately, combined therapy may have more side effects than single-agent treatment.
Nonetheless, identifying appropriate predictive biomarkers can aid in managing potential immune-related adverse events by distinguishing patients who respond best to PD-1 inhibitors as single agents or in combination strategies. In the present review, we summarize the therapeutic potential of PD-1 blockade therapy for advanced HCC patients. Besides, a glimpse of the pivotal predictive biomarkers influencing a patient's response to anti-PD-1 antibodies will be provided.
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