自然杀伤细胞（NK细胞）在抗肿瘤进展的先天免疫反应中发挥着不可或缺的作用。为了描绘它们在肿瘤微环境中的表型和功能多样性，我们对来自716名癌症患者的NK细胞进行了综合单细胞RNA测序分析，涵盖了24种癌症类型。我们观察到NK细胞组成存在特定于肿瘤类型的异质性。值得注意的是，我们已经确定了一群富集于肿瘤中的肿瘤相关NK细胞，它们表现出受损的抗肿瘤功能，并与不利的预后和免疫疗法抵抗力相关。特定的髓系细胞亚群，特别是LAMP3+树突状细胞，似乎介导了对NK细胞抗肿瘤免疫的调控。我们的研究揭示了NK细胞基于癌症免疫的相关洞见，并突显了NK细胞亚群作为治疗靶点的潜在临床用途。版权所有©2023 The Author(s). Elsevier Inc.保留所有权利。

Natural killer (NK) cells play indispensable roles in innate immune responses against tumor progression. To depict their phenotypic and functional diversities in the tumor microenvironment, we perform integrative single-cell RNA sequencing analyses on NK cells from 716 patients with cancer, covering 24 cancer types. We observed heterogeneity in NK cell composition in a tumor-type-specific manner. Notably, we have identified a group of tumor-associated NK cells that are enriched in tumors, show impaired anti-tumor functions, and are associated with unfavorable prognosis and resistance to immunotherapy. Specific myeloid cell subpopulations, in particular LAMP3+ dendritic cells, appear to mediate the regulation of NK cell anti-tumor immunity. Our study provides insights into NK-cell-based cancer immunity and highlights potential clinical utilities of NK cell subsets as therapeutic targets.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.