Turiello Roberta, Ng Susanna S, Tan Elisabeth, van der Voort Gemma, Salim Nazhifah, Yong Michelle C R, Khassenova Malika, Oldenburg Johannes, Rühl Heiko, Hasenauer Jan, Surace Laura, Toma Marieta, Bald Tobias, Hölzel Michael, Corvino Dillon
Institute of Experimental Oncology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany.
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Eur J Immunol. 2025 Jun;55(6):e51885. doi: 10.1002/eji.202551885.
Cytotoxicity is a cornerstone of immune defense, critical for combating tumors and infections. This process relies on the coordinated action of granzymes and pore-forming proteins, with granzyme B (GZMB) and perforin (PRF1) being key markers and the most widely studied molecules pertaining to cytotoxicity. However, other human granzymes and cytotoxic components remain underexplored, despite growing evidence of their distinct, context-dependent roles. Natural killer cell granule protein 7 (NKG7) has recently emerged as a crucial cytotoxicity regulator, yet its expression patterns and function are poorly understood. Using large publicly available single-cell RNA sequencing atlases, we performed a comprehensive profiling of cytotoxicity across immune subsets and tissues. Our analysis highlights NKG7 expression as a strong marker of cytotoxicity, exhibiting a strong correlation with overall cytotoxic activity (r = 0.97) and surpassing traditional markers such as granzyme B and perforin in reliability. Furthermore, NKG7 expression is notably consistent across diverse immune subsets and tissues, reinforcing its versatility and robustness as a cytotoxicity marker. These findings position NKG7 as an invaluable tool for evaluating immune responses and a reliable indicator of cytotoxic functionality across biological and clinical contexts.
细胞毒性是免疫防御的基石，对对抗肿瘤和感染至关重要。这一过程依赖于颗粒酶和穿孔素形成蛋白的协同作用，其中颗粒酶B（GZMB）和穿孔素（PRF1）是关键标志物，也是与细胞毒性相关研究最为广泛的分子。然而，尽管越来越多的证据表明其他人类颗粒酶和细胞毒性成分具有独特的、依赖于背景的作用，但它们仍未得到充分研究。自然杀伤细胞颗粒蛋白7（NKG7）最近已成为一种关键的细胞毒性调节因子，但其表达模式和功能仍知之甚少。利用公开的大型单细胞RNA测序图谱，我们对免疫亚群和组织中的细胞毒性进行了全面分析。我们的分析突出了NKG7表达作为细胞毒性的一个强标志物，与总体细胞毒性活性呈现出很强的相关性（r = 0.97），并且在可靠性方面超过了颗粒酶B和穿孔素等传统标志物。此外，NKG7表达在不同的免疫亚群和组织中显著一致，强化了其作为细胞毒性标志物的通用性和稳健性。这些发现使NKG7成为评估免疫反应的宝贵工具，以及在生物学和临床背景下细胞毒性功能的可靠指标。
