免疫检查点抑制剂在非小细胞肺癌（NSCLC）治疗中的疗效仍然有限。自然杀伤（NK）细胞作为先天免疫的关键元素，在抗肿瘤免疫中起着重要作用，探究NK细胞对NSCLC中抗PD-1治疗疗效的影响是值得探索的。我们分析了接受抗PD-1治疗的NSCLC患者活检组织中的单细胞转录组数据。鉴定了免疫细胞亚型，并进一步分析和验证了细胞间的相互通讯。我们观察到NSCLC浸润免疫细胞中完全有6个不同的NK细胞群。值得注意的是，应答组中富集了不成熟的NK细胞。一系列与不成熟NK细胞标记基因相关的基因与抗PD-1应答以及与抗原处理、Th1、Th17细胞激活等免疫调节过程相关。此外，应答组中的效应性CD8+ T细胞富集并且与不成熟NK细胞表现出类似的轨迹。细胞间通讯分析显示，不成熟NK细胞与Th17细胞和效应性CD8+ T细胞之间有强烈的互作。此外，在验证不成熟NK细胞标记基因的表达时，我们发现CXCR4与富集的CD8+ T细胞浸润相关。综上所述，不成熟NK细胞通过与Th1细胞、Th17细胞的相互作用以及增强效应性CD8+ T细胞的浸润可能有助于抗PD-1治疗的疗效。我们的数据表明，NK细胞可能是改善NSCLC患者预后的一个有希望的靶点。版权所有 © 2023. Elsevier B.V. 发表。

The efficacy of immune checkpoint inhibitors remains limited in non-small cell lung cancer (NSCLC). Natural killer (NK) cells serve as the key element of innate immunity and play an important role in anti-tumor immunity, the impact of NK cells on efficacy of anti-PD-1 therapy in NSCLC is worth exploring.We analyzed single-cell transcriptome data derived from biopsies of NSCLC patients receiving anti-PD-1 treatment. Immune cell subtypes were identified and further cell-cell communication were analyzed and verified.We observed totally 6 distinct NK cells clusters in NSCLC infiltrating immune cells. It's worth noting that enrichment of immature NK cells was found in responsive group. A series of marker genes of immature NK cells were associated with anti-PD-1 response and related to immune regulation processes such as antigen processing, Th1, Th17 cells activation. Moreover, effector CD8+ T cells were significantly enriched in responsive group and showed similar trajectories with immature NK cells. Cell-cell communication analysis showed that immature NK cells showed strong interactions with Th17 cells and effector CD8+ T cells. Furthermore, when validating the expression of immature NK cells marker genes, we found that CXCR4 was associated with enriched infiltration of CD8+ T cells.In conclusion, immature NK cells may facilitate the efficacy of anti-PD-1 therapy by interacting with Th1 cells, Th17 cells and enhancing infiltration of effector CD8+ T cells. Our data suggested that NK cells could be a promising target to improve the prognosis of NSCLC patients.Copyright © 2023. Published by Elsevier B.V.