Tumor stage-driven disruption of NK cell maturation in human and murine tumors
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.
Authors
- Maxime Meylan (ORCID: https://orcid.org/0000-0002-6175-1954)
- Isabelle Cremer (ORCID: https://orcid.org/0000-0002-0963-1031)
- Dan Sun (ORCID: https://orcid.org/0000-0003-2147-9308)
- Niklas K. Björkström (ORCID: https://orcid.org/0000-0002-0967-076X)
- Elodie Voilin
- Sophie Sibéril (ORCID: https://orcid.org/0000-0003-0184-2886)
- Nicolas S. Merle (ORCID: https://orcid.org/0000-0003-0379-7724)
- Carine Torset
- Solenne Marmier (ORCID: https://orcid.org/0000-0002-6671-0940)
- Marco Alifano
- Jules Russick (ORCID: https://orcid.org/0000-0001-7085-7614)
- Pierre-Emmanuel Foy (ORCID: https://orcid.org/0000-0003-1555-8624)
- Pierre-Emmanuel Joubert (ORCID: https://orcid.org/0000-0001-9859-6479)
- Audrey Lupo (ORCID: https://orcid.org/0009-0001-5398-5988)
- Diane Damotte (ORCID: https://orcid.org/0000-0001-5355-3045)
- Nathalie Josseaume (ORCID: https://orcid.org/0000-0002-3343-7941)
- Isaias Hernández-Verdín (ORCID: https://orcid.org/0000-0001-6295-2507)
Institutions
- Karolinska University Hospital (SE)
- Inserm (FR)
- Karolinska Institutet (SE)
- Sorbonne Université (FR)
- Centre de Recherche des Cordeliers (FR)
- Hôpital Cochin (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
Publication Details
- Journal
- iScience
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1016/j.isci.2024.111233
- Citations
- 4
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.96
Funders
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- Sorbonne Université
- Labex Immuno-Oncology