急性髓系白血病（AML）是一种常见的血液恶性肿瘤，即使通过强化化疗达到缓解，仍然常发生复发。已知的一种复发机制是白血病细胞逃脱免疫监视。目前，由于缺乏特异性抗原，尚无有效的AML免疫疗法。在这里，我们旨在阐明CD155和CD112在AML细胞系和原发AML样本中的关联及其治疗反应。简言之，我们生成了具有改变的nk-92细胞系（NK-92），这些细胞系具有修改的DNAM-1和T细胞免疫球蛋白及ITIM结构域（TIGIT），它们分别是CD155和CD112的受体。对200例AML病例的分析表明，CD112的高表达与存活时间较短相关。NK-92 DNAM-1对AML细胞系和原发AML患者细胞具有增强的细胞毒性活性。NK-92细胞中DNAM-1的诱导增强了与细胞毒性相关基因的表达，从而克服了TIGIT的抑制活性。在CD155和CD112之间，CD112是AML的NK细胞治疗的一个重要靶点。使用异种移植模型，我们证实了NK-92 DNAM-1相对于单独使用NK-92的增强抗肿瘤效果。我们还揭示了作为Nectin/Nectin-like家族的一员的免疫检查点分子CD112（Nectin-2）作为免疫治疗的新靶点。总之，修改NK细胞中的DNAM-1/CD112轴可能是治疗AML的有效新型免疫治疗。此外，这些结果提示这些分子的表达水平作为AML的预后标志物的潜力。

Acute myeloid leukemia (AML) is a hematological malignancy that frequently relapses, even if remission is achieved with intensive chemotherapy. One known relapse mechanism is the escape of leukemic cells from immune surveillance. Currently, there is no effective AML immunotherapy owing to the lack of specific antigens. Here, we aimed to elucidate the association between CD155 and CD112 in AML cell lines and primary AML samples and their therapeutic response. Briefly, we generated NK-92 cell lines (NK-92) with modified DNAX-associated molecule 1 (DNAM-1) and T-cell immunoglobulin and ITIM domain (TIGIT), which are receptors of CD155 and CD112, respectively. Analysis of 200 AML cases indicated that high expression of CD112 is associated with shorter survival than low expression. NK-92 DNAM-1 exhibited enhanced cytotoxic activity against AML cell lines and primary cells derived from patients with AML. DNAM-1 induction in NK-92 cells enhances the expression of cytotoxicity-related genes, thus overcoming TIGIT inhibitory activity. Between CD155 and CD112, CD112 is an especially important target for NK cell therapy of AML. Using a xenograft model, we confirmed the enhanced antitumor effect of NK-92 DNAM-1 compared with that of NK-92 alone. We also revealed that CD112 (Nectin-2), an immune checkpoint molecule belonging to the Nectin/Nectin-like family, functions as a novel target of immunotherapy. In conclusion, the modification of the DNAM-1/CD112 axis in NK cells may be an effective novel immunotherapy for AML. Furthermore, these results suggest the potential of the expression levels of these molecules as prognostic markers in AML.