Tumor stage-driven disruption of NK cell maturation in human and murine tumors

人类和鼠类肿瘤中肿瘤阶段驱动的 NK 细胞成熟破坏

阅读:2
作者:Jules Russick, Carine Torset, Dan Sun, Solenne Marmier, Nicolas Merle, Elodie Voilin, Nathalie Josseaume, Maxime Meylan, Isaïas Hernandez, Pierre-Emmanuel Foy, Pierre-Emmanuel Joubert, Marco Alifano, Audrey Lupo, Sophie Siberil, Niklas K Björkström, Diane Damotte, Isabelle Cremer

Abstract

Natural killer (NK) cells play a pivotal role against cancer, both by direct killing of malignant cells and by promoting adaptive immune response though cytokine and chemokine secretion. In the lung tumor microenvironment (TME), NK cells are scarce and dysfunctional. By conducting single-cell transcriptomic analysis of lung tumors, and exploring pseudotime, we uncovered that the intratumoral maturation trajectory of NK cells is disrupted in a tumor stage-dependent manner, ultimately resulting in the selective exclusion of the cytotoxic subset. Using functional assays, we observed intratumoral NK cell death and a reduction in cytotoxic capacities depending on the tumor stage. Finally, our analyses of human public dataset on lung cancer corroborate these findings, revealing a parallel dysfunctional maturation process of NK cells during tumor progression. These results highlight additional mechanisms by which tumor cells escape from NK cell cytotoxicity, therefore paving the way for tailored therapeutic strategies.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。