黑素瘤伴肝转移致免疫疗法疗效下降现象及其对策研究进展

Research progress in restrained immunotherapy efficacy for melanoma with liver metastasis and its countermeasures

恶性黑素瘤是一种临床常见的高度侵袭性肿瘤,致死率高、预后不良。早期的黑素瘤主要通过手术切除治疗,而晚期的黑素瘤目前更推荐使用靶向药物或免疫疗法治疗。晚期黑素瘤常伴发多种脏器转移,肝脏是其中常见脏器之一。大量临床研究及观察发现,不同于其它的脏器转移,黑素瘤患者发生肝转移时,免疫疗法的疗效显著下降。本文就这一有趣的临床现象及其可能的治疗对策进行综述。黑素瘤在合并肝转移时免疫疗法疗效的下降可能源于肝脏特殊的解剖结构及免疫组分的影响,以及肝脏存在转移瘤时肿瘤抗原特异性CD8+T细胞凋亡或活性下降,进而无法杀灭肿瘤细胞所致。免疫疗法联合肝定向放疗、过继性细胞治疗或靶向消除Treg细胞等方式可以部分纠正肝转移癌所致的免疫失衡,而最佳的治疗方案仍有待进一步探索。

Melanoma is a common malignant tumor,characterized by high fatality rate and poor prognosis.Early phase melanoma can be successfully treated by surgical resection,while targeted therapy or immunotherapy is mostly recommended for advanced melanoma.Advanced melanoma is often accompanied with multiple organ metastases,and most common in the liver.Numerous clinical studies show that in contrast to metastasis to other organs,the efficacy of immunotherapy is significantly reduced in melanoma patients with liver metastasis.This review discusses this interesting clinical phenomenon and its possible treatment strategies.The discrepancy in the efficacy of immunotherapy for liver metastatic melanoma may be related to the special anatomical structure and immune components of the liver.Liver metastasis can lead to the apoptosis or decreased activity of tumor antigen-specific CD8+T cells,which are crucial for killing tumor cells.Immunotherapy combined with liver-targeted radiotherapy,adoptive cell therapy,or targeted elimination of Treg cells may offer opportunities to correct the immune imbalance caused by liver metastasis.However,the optimal treatment plan remains to be further explored.