Krishnamurthy Shivani, Gilot David, Ahn Seong Beom, Lam Vincent, Shin Joo-Shik, Guillemin Gilles Jackie, Heng Benjamin
Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney 2109, Australia.
INSERM U1242, University of Rennes, 35000 Rennes, France.
Cancers (Basel). 2021 Oct 15;13(20):5180. doi: 10.3390/cancers13205180.
As the second and third leading cancer-related death in men and the world, respectively, primary liver cancer remains a major concern to human health. Despite advances in diagnostic technology, patients with primary liver cancer are often diagnosed at an advanced stage. Treatment options for patients with advanced hepatocarcinoma (HCC) are limited to systemic treatment with multikinase inhibitors and immunotherapy. Furthermore, the 5-year survival rate for these late-stage HCC patients is approximately 12% worldwide. There is an unmet need to identify novel treatment options and/or sensitive blood-based biomarker(s) to detect this cancer at an early stage. Given that the liver harbours the largest proportion of immune cells in the human body, understanding the tumour-immune microenvironment has gained increasing attention as a potential target to treat cancer. The kynurenine pathway (KP) has been proposed to be one of the key mechanisms used by the tumour cells to escape immune surveillance for proliferation and metastasis. In an inflammatory environment such as cancer, the KP is elevated, suppressing local immune cell populations and enhancing tumour growth. In this review, we collectively describe the roles of the KP in cancer and provide information on the latest research into the KP in primary liver cancer.
原发性肝癌分别是男性和全球第二和第三大癌症相关死因,仍然是人类健康的主要关注点。尽管诊断技术有所进步,但原发性肝癌患者往往在晚期才被诊断出来。晚期肝细胞癌(HCC)患者的治疗选择仅限于使用多激酶抑制剂进行全身治疗和免疫治疗。此外,这些晚期HCC患者的全球5年生存率约为12%。迫切需要确定新的治疗选择和/或基于血液的敏感生物标志物,以便在早期检测出这种癌症。鉴于肝脏中含有人体最大比例的免疫细胞,了解肿瘤免疫微环境作为治疗癌症的潜在靶点越来越受到关注。犬尿氨酸途径(KP)被认为是肿瘤细胞逃避免疫监视以进行增殖和转移的关键机制之一。在癌症等炎症环境中,KP升高,抑制局部免疫细胞群体并促进肿瘤生长。在这篇综述中,我们共同描述了KP在癌症中的作用,并提供了关于原发性肝癌中KP最新研究的信息。