Van Acker Heleen H, Van Acker Zoë P, Versteven Maarten, Ponsaerts Peter, Pende Daniela, Berneman Zwi N, Anguille Sébastien, Van Tendeloo Viggo F, Smits Evelien L
Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
Laboratory of Protein Science, Proteomics and Epigenetic Signaling, University of Antwerp, 2610 Antwerp, Belgium.
Cancers (Basel). 2019 Jul 22;11(7):1029. doi: 10.3390/cancers11071029.
A particularly interesting marker to identify anti-tumor immune cells is the neural cell adhesion molecule (NCAM), also known as cluster of differentiation (CD)56. Namely, hematopoietic expression of CD56 seems to be confined to powerful effector immune cells. Here, we sought to elucidate its role on various killer immune cells. First, we identified the high motility NCAM-120 molecule to be the main isoform expressed by immune cells. Next, through neutralization of surface CD56, we were able to (1) demonstrate the direct involvement of CD56 in tumor cell lysis exerted by CD56-expressing killer cells, such as natural killer cells, gamma delta (γδ) T cells, and interleukin (IL)-15-cultured dendritic cells (DCs), and (2) reveal a putative crosstalk mechanism between IL-15 DCs and CD8 T cells, suggesting CD56 as a co-stimulatory molecule in their cell-to-cell contact. Moreover, by means of a proximity ligation assay, we visualized the CD56 homophilic interaction among cancer cells and between immune cells and cancer cells. Finally, by blocking the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase (PI3K)-Akt pathway, we showed that IL-15 stimulation directly led to CD56 upregulation. In conclusion, these results underscore the previously neglected importance of CD56 expression on immune cells, benefiting current and future immune therapeutic options.
一种用于识别抗肿瘤免疫细胞的特别有趣的标志物是神经细胞黏附分子（NCAM），也称为分化簇（CD）56。也就是说，CD56的造血表达似乎局限于强大的效应免疫细胞。在此，我们试图阐明其在各种杀伤性免疫细胞上的作用。首先，我们确定高迁移率的NCAM-120分子是免疫细胞表达的主要异构体。接下来，通过中和表面CD56，我们能够（1）证明CD56直接参与表达CD56的杀伤细胞（如自然杀伤细胞、γδT细胞和白细胞介素（IL）-15培养的树突状细胞（DCs））对肿瘤细胞的裂解，以及（2）揭示IL-15 DCs和CD8 T细胞之间一种假定的串扰机制，表明CD56在它们的细胞间接触中作为共刺激分子。此外，通过邻近连接分析，我们观察到癌细胞之间以及免疫细胞与癌细胞之间的CD56同源相互作用。最后，通过阻断丝裂原活化蛋白激酶（MAPK）途径和磷酸肌醇3激酶（PI3K）-Akt途径，我们表明IL-15刺激直接导致CD56上调。总之，这些结果强调了免疫细胞上CD56表达先前被忽视的重要性，有利于当前和未来的免疫治疗选择。
