Valhondo Isabel, Hassouneh Fakhri, Lopez-Sejas Nelson, Pera Alejandra, Sanchez-Correa Beatriz, Guerrero Beatriz, Bergua Juan M, Arcos Maria Jose, Bañas Helena, Casas-Avilés Ignacio, Sanchez-Garcia Joaquin, Serrano Josefina, Martin Carmen, Duran Esther, Alonso Corona, Solana Rafael, Tarazona Raquel
Immunology Unit, University of Extremadura, 10003 Cáceres, Spain.
Department of Immunolgy and Allergy, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Cordoba, Spain.
Cancers (Basel). 2020 Aug 5;12(8):2171. doi: 10.3390/cancers12082171.
: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. : We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. : NK cells, CD56- T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56- T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1-TIGIT+TACTILE+ NK cells and DNAM-1- TIGIT+TACTILE+ CD56- T cells were associated with a better survival of AML patients. : The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.
急性髓系白血病（AML）由于总体生存率低，仍然是一个重大的临床挑战，在老年患者中情况更为严峻。TIGIT是一种与CD155和CD112分子相互作用的抑制性受体，被认为是T细胞和自然杀伤（NK）细胞激活的一个检查点。该受体与共刺激受体DNAM-1以及TACTILE共享配体。这项工作的目的是分析AML患者NK细胞和T细胞亚群中DNAM-1、TIGIT和TACTILE的表达情况。
我们研究了36例AML诊断时的患者和20名健康志愿者。根据CD3和CD56的表达情况，通过流式细胞术检测NK细胞和T细胞中DNAM-1、TIGIT和TACTILE的表达。
与健康志愿者相比，AML患者的NK细胞、CD56-T细胞和CD56+T（NKT样）细胞中DNAM-1的表达降低。在主流CD56-T细胞中观察到TIGIT表达增加。未观察到TACTILE表达的差异。对DNAM-1、TIGIT和TACTILE共表达的简化复杂评估分析（SPICE分析）显示，缺乏DNAM-1并共表达TIGIT和TACTILE的NK细胞和T细胞增加。低比例缺乏DNAM-1、TIGIT+TACTILE+的NK细胞和DNAM-1-TIGIT+TACTILE+的CD56-T细胞与AML患者更好的生存率相关。
与健康志愿者相比，AML患者的NK细胞以及CD4+和CD8+T细胞中DNAM-1的表达降低。缺乏DNAM-1并共表达TIGIT和TACTILE的NK细胞和T细胞比例增加与患者生存率相关，支持TIGIT作为检查点阻断新候选者的作用。
