恶性黑素瘤免疫逃逸机制与对策

Recent advances in melanoma vaccine research： mechanisms of tumor evasion and strategies for breaking tolerance

恶性黑素瘤治疗困难，免疫治疗是治疗本病的新型策略，治疗性疫苗则是其最为重要的形式。目前黑素瘤治疗性疫苗开发远未成功，究其原因与肿瘤具有多种免疫逃逸机制有关，主要包括两类：①肿瘤低免疫原性、肿瘤相关抗原及MHC Ⅰ类分子表达缺失、免疫隔离等所导致的免疫识别障碍；②抑制性树突状细胞、PD-1等抑制性配体、调节性T细胞、抑制性细胞因子等造成的免疫效应障碍。对其深入研究有利于开发更为合理有效的对策。

Malignant melanoma remains a management challenge. Immunotherapy is a promising strategy for the treatment of melanoma, and therapeutic vaccination is the most important form of active specific immunotherapy. To date, development of melanoma vaccines are far from success. The reason might lie in the increasingly documented facts that tumors develop diverse immune escape strategies, including： 1.immune ignorance caused by low immunogenicity of melanoma, loss of tumor-associated antigens, absence of MHC class Ⅰ molecule expression, and immune isolation due to the lack of some adhesion molecules; 2.immune tolerance caused by suppressive dendritic cells, ligands of coinhibitory receptors, regulatory T cells, suppressive cytokines, and so on. Despite these obstacles, several strategies have been developed for effective tumor immunity.