非热等离子体（NTP）有望成为一种有效的抗癌疗法，具有细胞毒性和免疫调节作用。在这项研究中，我们研究了 NTP 诱导的氧化对自然杀伤 (NK) 细胞功能的几个关键、决定性免疫检查点的化学和生物效应。我们使用分子动力学 (MD) 和伞式采样模拟来研究 NTP 诱导的氧化变化对 MHC-I 复合物 HLA-Cw4 和 HLA-E 的影响。我们的模拟表明，这些化学变化不会显着影响这些标记物与其相应 NK 细胞受体的结合亲和力，这得到了 NTP 应用后人头颈鳞状细胞癌细胞上配体表达的实验读数的支持。将我们的范围扩大到 NK 细胞反应性的其他关键配体，我们证明了治疗后 CD155 和 CD112（抑制性 TIGIT 轴的靶配体）以及免疫检查点 CD73 的快速减少。除了这些短暂的化学变化之外，NTP 中的活性物质还会引起一系列下游细胞反应。治疗后 24 小时，应激蛋白 MICA/B（NK 细胞激活的有效配体）的上调强调了这一点。总而言之，这项工作证实了 NTP 的免疫调节潜力，并揭示了 NTP 与癌细胞之间的相互作用机制。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Non-thermal plasma (NTP) shows promise as a potent anti-cancer therapy with both cytotoxic and immunomodulatory effects. In this study, we investigate the chemical and biological effects of NTP-induced oxidation on several key, determinant immune checkpoints of natural killer (NK) cell function. We used molecular dynamics (MD) and umbrella sampling simulations to investigate the effect of NTP-induced oxidative changes on the MHC-I complexes HLA-Cw4 and HLA-E. Our simulations indicate that these chemical alterations do not significantly affect the binding affinity of these markers to their corresponding NK cell receptor, which is supported with experimental read-outs of ligand expression on human head and neck squamous cell carcinoma cells after NTP application. Broadening our scope to other key ligands for NK cell reactivity, we demonstrate rapid reduction in CD155 and CD112, target ligands of the inhibitory TIGIT axis, and in immune checkpoint CD73 immediately after treatment. Besides these transient chemical alterations, the reactive species in NTP cause a cascade of downstream cellular reactions. This is underlined by the upregulation of the stress proteins MICA/B, potent ligands for NK cell activation, 24 h post treatment. Taken together, this work corroborates the immunomodulatory potential of NTP, and sheds light on the interaction mechanisms between NTP and cancer cells.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.