PD-1阻断T细胞活化信号，降低CD8+T杀伤瘤细胞能力；而癌基因EZH2可抑制瘤细胞合成T细胞趋化因子CXCL9/10，使瘤体中CD8+T数量显著减少；卵巢癌中证实，PD-1抗体（活化CD8+T）联合EZH2拮抗剂（增加CD8+T数量）对瘤细胞杀伤力明显优于单纯PD-1抗体组。本课题组前期实验发现具有拮抗EZH2能力的天然中药单体雷公藤内酯醇，可显著抑制MM细胞表达EZH2，同时预实验运用shRNA技术证实，EZH2活性极可能受MEG3lncRNA以直接结合的方式调控。因此我们大胆推测，雷公藤内酯醇通过促进MEG3lncRNA与EZH2结合形成复合物，阻断EZH2催化H3K27的甲基化酶活性位点， CXCL9/10启动子H3K27me3表达减弱，CXCL9/10转录激活，趋化CD8+T瘤体浸润。本研究可为临床雷公藤内酯醇与PD-1抗体联合免疫治疗MM提供有力理论基础，具有重大临床意义。

PD-1 block activating signals of T cell, reduce the ability of CD8+T cells to kill tumor cells; EZH2 significantly reduce the number of CD8+T cells by inhibiting tumor cells from producing chemokine CXCL9/10, the number of CD8+T cells reduced in the tumors; Confirmed in ovarian cancer, PD-1 antibodies (activating CD8+T cells) joint EZH2 antagonists (to increase the number of CD8+T cells) kill more tumor cells more than PD-1 antibody only. Our previous experiments found that triptolide which is natural monomer of Chinese medicine capable of antagonizing EZH2, triptolide could inhibit the expression of EZH2 significantly in MM cell, at the same time, preliminary experiment using shRNA technology confirmed that EZH2 activity would most likely be regulated by MEG3-lncRNA through combining with EZH2 directly. So we speculate, triptolide would like block EZH2 catalytic activity of tri-methylate H3K27 by promoting MEG3-lncRNA forming complex with EZH2, then the expression of H3K27me3 on CXCL9/10 promoter abate, CXCL9/10 transcription activation, attract CD8+T cells to tumors. This study could provide strong theoretical foundation of triptolide combining with PD-1 antibody for immunotherapy of MM, the subject is significant for clinic.