提吉特
髓系白血病
免疫疗法
癌症研究
细胞毒性T细胞
免疫系统
免疫学
髓样
白血病
医学
生物
生物化学
体外
作者
Yuta Kaito,Emi Sugimoto,Fumi Nakamura,Yutaka Tsukune,Makoto Sasaki,Shunsuke Yui,Hiroki Yamaguchi,Susumu Goyama,Yasuhito Nannya,Kinuko Mitani,Hideto Tamura,Yoichi Imai
标识
DOI:10.3324/haematol.2023.282915
摘要
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.
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