Sankar Kamya, Pearson Ashley N, Worlikar Tejaswi, Perricone Matthew D, Holcomb Erin A, Mendiratta-Lala Mishal, Xu Zhen, Bhowmick Neil, Green Michael D
Division of Medical Oncology, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Graduate Program in Immunology, School of Medicine, University of Michigan, Ann Arbor, MI, USA.
Transl Gastroenterol Hepatol. 2023 Jun 27;8:29. doi: 10.21037/tgh-23-11. eCollection 2023.
The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.
肝脏是一个功能独特的器官，具有免疫抑制性微环境。肝脏是人类原发性癌症的第六大常见部位，也是其他实体瘤常见的转移部位。由于肝脏复杂的代谢和免疫微环境，开发针对原发性和转移性肝癌的有效疗法一直具有挑战性。原发性和继发性（转移性）肝癌中的肝脏肿瘤微环境（TME）是异质性的，由独特的免疫和基质细胞群体组成。这些细胞群体与肿瘤细胞之间的相互作用在肝脏内形成了免疫抑制性微环境，从而促进癌症进展。免疫检查点抑制剂（ICIs）目前已在临床上被批准用于原发性和继发性肝癌的治疗，并且可以部分克服肝脏免疫耐受，但其疗效有限。在这篇综述中，我们描述了肝脏微环境以及免疫疗法在原发性和继发性肝癌中的应用。我们讨论了利用局部区域和全身治疗方法的新兴联合策略，这些策略可能会提高免疫疗法在原发性和继发性肝癌中的疗效。对肝脏免疫抑制性微环境的更深入了解将为新型疗法和治疗组合提供依据，以改善原发性和继发性肝癌患者的治疗结果。
