非小细胞肺癌肝转移免疫微环境及未来干预策略

Immune microenvironment for liver metastasis of non-small cell lung cancer and future intervention strategies

肺癌是发病率和死亡率最高的恶性肿瘤,约有75%以上患者在诊断时已是晚期。肝转移是肺癌患者预后差的重要原因,约有20%的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者会发生肝转移。近几年,免疫检查点抑制剂(immune checkpoint inhibitors,ICI)单药和联合治疗在晚期NSCLC患者取得了突破性进展。临床研究提示,肝转移患者亦可从ICI治疗中获益,但相较于整体人群,肝转移仍然是免疫治疗效果差的独立预后因素。因此,深入探索肝转移患者的免疫微环境,对提高这部分人群的生存预后具有重要意义。肿瘤微环境(tumor microenvironment,TME)表型是决定免疫治疗效果的关键因素,不同器官的TME具有特异性,可能是其免疫疗效差异的重要原因所在。肝脏中的多种细胞成分相互作用,构成了复杂的免疫微环境,共同参与肝脏的免疫调节。因此,聚焦于肝脏免疫微环境,并结合免疫治疗最新进展,对NSCLC肝转移的国内外研究进展进行总结,以期为确立肝转移患者治疗新策略提供线索。

Lung cancer is the tumor with the highest morbidity and mortality.About 75%of patients are already in the advanced stage at the time of diagnosis.Liver metastasis is an important factor leading to the poor prognosis of lung cancer patients.About 20% of patients with non-small cell lung cancer(NSCLC)will develop liver metastases.In recent years,immune checkpoint inhibitors(ICI)monotherapy and combination therapy have made breakthrough progress in patients with advanced NSCLC.Clinical studies suggested that patients with liver metastases could also benefit from ICI therapy,however compared to the overall population,liver metastasis was still an independent prognostic factor for poor efficacy of immunotherapy.Therefore,exploration of the resistance mechanism of patients with liver metastases is of great significance to improve the survival prognosis of this population.Tumor microenvironment(TME)phenotype is a key factor in determining the efficacy of immunotherapy.The specific difference in TME among different organs may be an important reason for their different responses to immunotherapy.A variety of cellular components in the liver interact to form its complex immune microenvironment and participate in the immune regulation of the liver.Therefore,this article was intended to focus on the liver immune microenvironment and the latest progress in immunotherapy to summarize the domestic and foreign research progress in NSCLC liver metastasis.We hope to provide novel insights for the development of new treatment strategies for patients with liver metastases.