分子靶向－过继性细胞免疫治疗是分子靶向药物和过继性细胞免疫疗法有机结合的新治疗模式，该模式建立在NK细胞活化性信号通路(NKG2DNKG2DLs) 的生物学特性，尤其是受配体可调控性的理论基础之上。分子靶向药物在其中扮演双重角色，除了药物本身对肿瘤细胞的毒性作用外，还作为“刺激诱导”源，诱导肿瘤细胞表达免疫激活物NKG2DLs（natural killer group 2 member D ligands），与NK细胞表面NKG2D（natural killer group 2 member D）结合，激活NK细胞的杀伤活性。NKG2D与NKG2DLs是NK细胞主要的活化性受、配体，在机体抗肿瘤免疫中起重要作用。NKG2D主要表达于NK、CD8+T、γδT和活化的巨噬细胞，参与适应性及固有性免疫应答。与NKG2D结合的配体(NKG2DLs)广泛低表达于多种肿瘤细胞，而在正常组织细胞几乎未见表达，靶细胞的NKG2DLs表达水平直接关系到免疫效应细胞（NK、DC、CTL细胞等）对其的杀伤活性。NKG2DLs的转录与表达可受多种因素影响，分子靶向药物可以诱导肿瘤细胞高表达NKG2DLs,NK细胞对高表达NKG2DLs的肿瘤细胞有较高杀伤活性，而对正常组织无杀伤作用，具有杀伤靶向性；NKG2DLs的高表达也增强了肿瘤细胞对其他免疫效应细胞的杀伤敏感性，具有良好的应用前景。分子靶向药物联合过继性细胞免疫治疗将使肿瘤患者获得更好的临床疗效，预示了肿瘤生物治疗新的发展方向——分子靶向-过继性细胞免疫治疗新模式的来临。

As a promising new strategy for cancer biotherapy, combined therapy of molecular targeted agents and adoptive cellular immunotherapy is established based on the biological characteristics of NK cell activating signal pathway (natural killer group 2 member Dnatural killer group 2 member D ligand, NKG2DNKG2DLs), especially its regulable ligand and receptor theory. Molecular targeted agents play dual functions: in addition to their toxic effects against tumor cells, they can also induce expression of NKG2D ligands on tumor cells, resulting in enhanced immune eradication of NK cells. As a pivotal activating receptor for NK cells, NKG2D and its ligands play important roles in the antitumor immune system, especially adoptive cellmediated immune response. NKG2D is mainly expressed by NK cells, CD8+T cells, γδ T cells and activated macrophages. As for NKG2D ligands, they have restricted expressions in normal tissues, but are frequently expressed on primary tumors. Therefore, expressions of these ligands are closely related to the antitumor effect of immune cells, without damage to the normal tissues. NKG2D ligands can be regulated by multiple stimuli including molecular targeted agents. The immunoregulation induced by molecular targeted agents through NKG2DNKG2DLs pathway has been shown valuable both for its distinguished targeting effects and for its wellestablished regulating effects. In summary, combination of molecular targeted agents and adoptive cellular immunotherapy may represent a bright future for tumor biotherapy.

国家自然科学基金资助项目（No. 30973454）；广东省自然科学基金重点项目（No. 9251051501000007）