Tumor stage-driven disruption of NK cell maturation in human and murine lung tumors - Sorbonne Université
Article Dans Une Revue iScience Année : 2024

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

Perturbation de la maturation des cellules NK en fonction du stade tumoral dans les tumeurs pulmonaires humaines et murines

Résumé

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.
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Dates et versions

hal-04843712 , version 1 (17-12-2024)

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Jules Russick, Carine Torset, Dan Sun, Solenne Marmier, Nicolas Merle, et al.. Tumor stage-driven disruption of NK cell maturation in human and murine lung tumors. iScience, 2024, 27 (11), pp.111233. ⟨10.1016/j.isci.2024.111233⟩. ⟨hal-04843712⟩
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