Montagner Annapaola, Arleo Andrea, Suzzi Fabrizia, D'Assoro Antonino B, Piscaglia Fabio, Gramantieri Laura, Giovannini Catia
Department of Medical and Surgical Sciences, Bologna University, 40138 Bologna, Italy.
Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
Biomolecules. 2024 Dec 11;14(12):1581. doi: 10.3390/biom14121581.
Immunotherapy has shown significant improvement in the survival of patients with hepatocellular carcinoma (HCC) compared to TKIs as first-line treatment. Unfortunately, approximately 30% of HCC exhibits intrinsic resistance to ICIs, making new therapeutic combinations urgently needed. The dysregulation of the Notch signaling pathway observed in HCC can affect immune cell response, reducing the efficacy of cancer immunotherapy. Here, we provide an overview of how Notch signaling regulates immune responses and present the therapeutic rationale for combining Notch signaling inhibition with ICIs to improve HCC treatment. Moreover, we propose using exosomes as non-invasive tools to assess Notch signaling activation in hepatic cancer cells, enabling accurate stratification of patients who can benefit from combined strategies.
与作为一线治疗的酪氨酸激酶抑制剂（TKIs）相比，免疫疗法已显著提高了肝细胞癌（HCC）患者的生存率。不幸的是，约30%的HCC对免疫检查点抑制剂（ICIs）表现出内在抗性，因此迫切需要新的治疗组合。在HCC中观察到的Notch信号通路失调可影响免疫细胞反应，降低癌症免疫疗法的疗效。在此，我们概述了Notch信号如何调节免疫反应，并提出将Notch信号抑制与ICIs联合以改善HCC治疗的理论依据。此外，我们建议使用外泌体作为非侵入性工具来评估肝癌细胞中Notch信号的激活，从而能够对可从联合策略中获益的患者进行准确分层。
