iScience (Nov 2024)
Tumor stage-driven disruption of NK cell maturation in human and murine tumors
- 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
Affiliations
- Jules Russick
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Carine Torset
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Dan Sun
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Solenne Marmier
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Nicolas Merle
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Elodie Voilin
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Nathalie Josseaume
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Maxime Meylan
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Isaïas Hernandez
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Pierre-Emmanuel Foy
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Pierre-Emmanuel Joubert
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Marco Alifano
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France; Departments of Surgery and Pathology, Hopital Cochin Assistance Publique Hopitaux de Paris, 75014 Paris, France
- Audrey Lupo
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France; Departments of Surgery and Pathology, Hopital Cochin Assistance Publique Hopitaux de Paris, 75014 Paris, France
- Sophie Siberil
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France
- Niklas K. Björkström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
- Diane Damotte
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France; Departments of Surgery and Pathology, Hopital Cochin Assistance Publique Hopitaux de Paris, 75014 Paris, France
- Isabelle Cremer
- INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Team “Inflammation, Complement and Cancer”, 75006 Paris, France; Sorbonne Universite, Centre de Recherche des Cordeliers, 75006 Paris, France; Universite Paris Cite, Centre de Recherche des Cordeliers, 75006 Paris, France; Corresponding author
- Journal volume & issue
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Vol. 27,
no. 11
p. 111233
Abstract
Summary: 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.
