Zeng Xuezhen, Ward Simon E, Zhou Jingying, Cheng Alfred S L
Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Cancers (Basel). 2021 May 17;13(10):2418. doi: 10.3390/cancers13102418.
A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.
患有局限性癌症的结直肠癌患者与发生远端器官转移的患者的5年生存率存在巨大差异。肝脏是结直肠癌转移最常见的器官。除了结直肠与肝脏的解剖关系外，新出现的证据凸显了肝脏免疫微环境对结直肠癌肝转移的影响。在癌细胞播散之前，肝细胞分泌多种因子来募集或激活肝脏中的免疫细胞和基质细胞，以形成有利的前转移微环境。包括库普弗细胞、肝星状细胞和肝窦内皮细胞在内的肝脏驻留细胞被募集来的细胞（如髓系来源的抑制细胞和肿瘤相关巨噬细胞）利用，以建立适合肿瘤细胞定植和生长的免疫抑制性肝脏微环境。目前的治疗方法，包括根治性手术、全身治疗和局部治疗，仅在少数结直肠癌肝转移患者中取得了良好的临床效果，高复发率进一步阻碍了治疗效果。更好地了解易发生转移的肝脏免疫微环境的调控机制，应为肝转移干预开辟新的免疫肿瘤学途径。
