Статья

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

Jules RussickCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FrancePierre-Emmanuel JoubertUniversité Paris CitéMélanie Gillard-BocquetCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceCarine TorsetCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceMaxime MeylanCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceFlorent PetitprezProgramme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, FranceMarie‐Agnès Dragon‐DureyCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceSolenne MarmierCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceAditi VarthamanCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceNathalie JosseaumeSorbonne UniversitéClaire GermainCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceJérémy GocCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceMarie‐Caroline Dieu‐NosjeanSorbonne Universite, INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses, Team Immune Microenvironment and Immunotherapy, F-75013, Paris, FrancePierre ValidireDepartment of Pathology, Institut Mutualiste Montsouris, Paris, FranceLudovic FournelDepartments of Pathology and Thoracic Surgery, Hospital Cochin Assistance Publique Hopitaux de Paris, F-75014, Paris, FranceLaurence ZitvogelINSERM U1015, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, FranceGabriela BindeaCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Laboratory of Integrative cancer immunology, F-75006, Paris, FranceAudrey Mansuet‐LupoCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceDiane DamotteCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceMarco AlifanoCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceIsabelle CremerCentre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France

2020en

ABI

Аннотация

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.

Перевод пока недоступен

Идентификаторы

DOI: 10.1136/jitc-2020-001054

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar