Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Journal for Immunotherapy of Cancer Année : 2020

Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions

Résumé

Background Natural killer (NK) cells play a crucial role in tumor immunosurveillance through their cytotoxic effector functions and their capacity to interact with other immune cells to build a coordinated antitumor immune response. Emerging data reveal NK cell dysfunction within the tumor microenvironment (TME) through checkpoint inhibitory molecules associated with a regulatory phenotype. Objective We aimed at analyzing the gene expression profile of intratumoral NK cells compared with non-tumorous NK cells, and to characterize their inhibitory function in the TME. Methods NK cells were sorted from human lung tumor tissue and compared with non- tumoral distant lungs. Results In the current study, we identify a unique gene signature of NK cell dysfunction in human non-small cell lung carcinoma (NSCLC). First, transcriptomic analysis reveals significant changes related to migratory pattern with a downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) and CX3C chemokine receptor 1 (CX3CR1) and overexpression of C-X-C chemokine receptor type 5 (CXCR5) and C-X-C chemokine receptor type 6 (CXCR6). Second, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and killer cell lectin like receptor (KLRC1) inhibitory molecules were increased in intratumoral NK cells, and CTLA-4 blockade could partially restore MHC class II level on dendritic cell (DC) that was impaired during the DCs/NK cell cross talk. Finally, NK cell density impacts the positive prognostic value of CD8 + T cells in NSCLC. Conclusions These findings demonstrate novel molecular cues associated with NK cell inhibitory functions in NSCLC.
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Dates et versions

inserm-03975406 , version 1 (06-02-2023)

Identifiants

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Jules Russick, Pierre-Emmanuel Joubert, Mélanie Gillard-Bocquet, Carine Torset, Maxime Meylan, et al.. Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions. Journal for Immunotherapy of Cancer, 2020, 8 (2), pp.e001054. ⟨10.1136/jitc-2020-001054⟩. ⟨inserm-03975406⟩
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