Kim Jieun, Seki Ekihiro
Karsh Division of Gastroenterology Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
Mol Cancer Ther. 2025 Feb 4;24(2):188-199. doi: 10.1158/1535-7163.MCT-23-0726.
Over the past two decades, the "hallmarks of cancer" have revolutionized cancer research and highlighted the crucial roles of inflammation and immunity. Protumorigenic inflammation promotes cancer development along with inhibition of antitumor immunity, shaping the tumor microenvironment (TME) toward a tumor-permissive state and further enhancing the malignant potential of cancer cells. This immunosuppressive TME allows tumors to evade immunosurveillance. Thus, understanding the complex interplay between tumors and the immune system within the TME has become pivotal, especially with the advent of immunotherapy. Although immunotherapy has achieved notable success in many malignancies, primary liver cancer, particularly hepatocellular carcinoma, presents unique challenges. The hepatic immunosuppressive environment poses obstacles to the effectiveness of immunotherapy, along with high mortality rates and limited treatment options for patients with liver cancer. In this review, we discuss current understanding of the complex immune-mediated mechanisms underlying liver neoplasms, focusing on hepatocellular carcinoma and liver metastases. We describe the molecular and cellular heterogeneity within the TME, highlighting how this presents unique challenges and opportunities for immunotherapy in liver cancers. By unraveling the immune landscape of liver neoplasms, this review aims to contribute to the development of more effective therapeutic interventions, ultimately improving clinical outcomes for patients with liver cancer.
在过去二十年中，“癌症标志”彻底改变了癌症研究，并突出了炎症和免疫的关键作用。促肿瘤炎症与抗肿瘤免疫抑制一起促进癌症发展，将肿瘤微环境（TME）塑造成有利于肿瘤的状态，并进一步增强癌细胞的恶性潜能。这种免疫抑制性TME使肿瘤能够逃避免疫监视。因此，了解TME内肿瘤与免疫系统之间的复杂相互作用已变得至关重要，尤其是随着免疫疗法的出现。尽管免疫疗法在许多恶性肿瘤中取得了显著成功，但原发性肝癌，尤其是肝细胞癌，却带来了独特的挑战。肝脏免疫抑制环境对免疫疗法的有效性构成障碍，同时肝癌患者的死亡率高且治疗选择有限。在这篇综述中，我们讨论了目前对肝脏肿瘤复杂免疫介导机制的理解，重点关注肝细胞癌和肝转移瘤。我们描述了TME内的分子和细胞异质性，强调了这如何给肝癌免疫疗法带来独特的挑战和机遇。通过揭示肝脏肿瘤的免疫格局，本综述旨在促进更有效的治疗干预措施的发展，最终改善肝癌患者的临床结局。
