Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
Department of Clinical Therapeutics, Alexandra University Hospital, Athens, Greece.
Adv Exp Med Biol. 2020;1296:227-241. doi: 10.1007/978-3-030-59038-3_14.
The tumor microenvironment (TME) has recently been recognized as an important part of tumor development and growth. TME is a dynamic system orchestrated by immune, cancer and inflammatory cells, as well as the stromal tissue and surrounding extracellular matrix. While TME of primary hepatic tumors is usually characterized by a strong inflammatory background, the TME of liver metastases typically consists of otherwise healthy liver tissue. Chronic inflammation and hypoxia are key to the development and progression of primary liver cancer. The injury caused by chronic inflammation creates a condition of immune evasion that initiates a cascade of events that eventually leads to liver carcinogenesis.With liver metastases, primary tumors "prime" the target organs via secreting factors that induce expansion of myeloid cell populations and create a solid ground for successful cancer settlement. Once in the liver, metastatic cells begin a neovascularization process that is driven mainly by VEGF and FGF. Due to high mortality rates associated with liver cancer, as well as the limited effective treatment options for advanced disease, new therapies are urgently needed. Targeting a single molecule in a number of interactions between the tumor and the TME is highly unlikely to reduce tumor growth. Future trials should focus on combination therapies (i.e. targeted therapies combined with immunotherapy) to treat liver malignancies efficiently.
肿瘤微环境（TME）最近被认为是肿瘤发生和生长的重要组成部分。TME 是一个由免疫、癌症和炎症细胞以及基质组织和周围细胞外基质协调的动态系统。虽然原发性肝肿瘤的 TME 通常以强烈的炎症背景为特征，但肝转移的 TME 通常由其他健康的肝组织组成。慢性炎症和缺氧是原发性肝癌发展和进展的关键。慢性炎症引起的损伤创造了一种免疫逃避的状态，引发了一系列事件，最终导致肝癌发生。对于肝转移，原发肿瘤通过分泌因子“启动”靶器官，诱导髓样细胞群体扩张，并为癌症成功定居创造坚实基础。一旦进入肝脏，转移性细胞开始血管生成过程，主要由 VEGF 和 FGF 驱动。由于肝癌的死亡率高，以及晚期疾病的有效治疗选择有限，因此迫切需要新的治疗方法。针对肿瘤与 TME 之间的许多相互作用中的单个分子不太可能减少肿瘤生长。未来的试验应集中于联合治疗（即靶向治疗联合免疫治疗），以有效治疗肝恶性肿瘤。
