Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions
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 microenvi...
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| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001054.full |
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| author | Diane Damotte Laurence Zitvogel Marco Alifano Marie-Caroline Dieu-Nosjean Gabriela Bindea Jeremy Goc Jules Russick Pierre-Emmanuel Joubert Mélanie Gillard-Bocquet Carine Torset Maxime Meylan Florent Petitprez Marie-Agnes Dragon-Durey Solenne Marmier Aditi Varthaman Nathalie Josseaume Claire Germain Pierre Validire Ludovic Fournel Audrey Lupo Isabelle Cremer |
| author_facet | Diane Damotte Laurence Zitvogel Marco Alifano Marie-Caroline Dieu-Nosjean Gabriela Bindea Jeremy Goc Jules Russick Pierre-Emmanuel Joubert Mélanie Gillard-Bocquet Carine Torset Maxime Meylan Florent Petitprez Marie-Agnes Dragon-Durey Solenne Marmier Aditi Varthaman Nathalie Josseaume Claire Germain Pierre Validire Ludovic Fournel Audrey Lupo Isabelle Cremer |
| author_sort | Diane Damotte |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-66cfd0aa9b7a4ab3ad675fae3785d405 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-66cfd0aa9b7a4ab3ad675fae3785d4052025-08-20T02:13:20ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001054Natural killer cells in the human lung tumor microenvironment display immune inhibitory functionsDiane Damotte0Laurence Zitvogel1Marco Alifano2Marie-Caroline Dieu-Nosjean3Gabriela Bindea4Jeremy Goc5Jules Russick6Pierre-Emmanuel Joubert7Mélanie Gillard-Bocquet8Carine Torset9Maxime Meylan10Florent Petitprez11Marie-Agnes Dragon-Durey12Solenne Marmier13Aditi Varthaman14Nathalie Josseaume15Claire Germain16Pierre Validire17Ludovic Fournel18Audrey Lupo19Isabelle Cremer201 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France8 Universite Paris Saclay, Le Kremlin-Bicêtre, FranceDepartment of Thoracic Surgery, Hospital Cochin Assistance Publique Hopitaux de Paris, APHP, Paris, Île-de-France, FranceSorbonne University, UMRS 1135, INSERM U1135, Centre d`Immunologie et des Maladies Infectieuses (Cimi-Paris), INSERM, Paris, Île-de-France, FranceAff142 grid.10992.330000000121880914INSERM, Université Pierre et Marie CurieUniversité Paris Descartes Paris FranceAff8 grid.417925.cINSERM, U1138, Centre de Recherche des Cordeliers Paris France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceEquipe inflammation, complément et cancer, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris-Cité, Paris, France2 Programme Cartes d`Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, France5 Department of Pathology, Institut Mutualiste Montsouris, Paris, France6 Departments of Pathology and Thoracic Surgery, Hospital Cochin Assistance Publique Hopitaux de Paris, F-75014, Paris, France1 Centre de Recherche des Cordeliers, Sorbonne Universite, Inserm, Universite de Paris, Team Inflammation, complement and cancer, F-75006, Paris, FranceINSERM U1138, Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Université, 75006 Paris, FranceBackground 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.https://jitc.bmj.com/content/8/2/e001054.full |
| spellingShingle | Diane Damotte Laurence Zitvogel Marco Alifano Marie-Caroline Dieu-Nosjean Gabriela Bindea Jeremy Goc Jules Russick Pierre-Emmanuel Joubert Mélanie Gillard-Bocquet Carine Torset Maxime Meylan Florent Petitprez Marie-Agnes Dragon-Durey Solenne Marmier Aditi Varthaman Nathalie Josseaume Claire Germain Pierre Validire Ludovic Fournel Audrey Lupo Isabelle Cremer Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions Journal for ImmunoTherapy of Cancer |
| title | Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| title_full | Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| title_fullStr | Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| title_full_unstemmed | Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| title_short | Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| title_sort | natural killer cells in the human lung tumor microenvironment display immune inhibitory functions |
| url | https://jitc.bmj.com/content/8/2/e001054.full |
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