Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia
Natural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1927 |
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| author | Dhon Roméo Makanga Francesca Da Rin de Lorenzo Gaëlle David Catherine Willem Léa Dubreuil Nolwenn Legrand Thierry Guillaume Pierre Peterlin Amandine Lebourgeois Marie Christine Béné Alice Garnier Patrice Chevallier Ketevan Gendzekhadze Anne Cesbron Katia Gagne Béatrice Clemenceau Christelle Retière |
| author_facet | Dhon Roméo Makanga Francesca Da Rin de Lorenzo Gaëlle David Catherine Willem Léa Dubreuil Nolwenn Legrand Thierry Guillaume Pierre Peterlin Amandine Lebourgeois Marie Christine Béné Alice Garnier Patrice Chevallier Ketevan Gendzekhadze Anne Cesbron Katia Gagne Béatrice Clemenceau Christelle Retière |
| author_sort | Dhon Roméo Makanga |
| collection | DOAJ |
| description | Natural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-leukemic potential of NK cell subsets, taking into account these genetic parameters and cytomegalovirus (CMV) status. Hierarchical clustering analysis of NK cell subsets based on NKG2A, KIR, CD57 and NKG2C markers from 68 blood donors identified donor clusters characterized by a specific phenotypic NK cell repertoire linked to a particular immunogenetic KIR and HLA profile and CMV status. On the functional side, acute lymphoblastic leukemia (ALL) was better recognized by NK cells than acute myeloid leukemia (AML). However, a broad inter-individual disparity of NK cell responses exists against the same leukemic target, highlighting bad and good NK responders. The most effective NK cell subsets against different ALLs expressed NKG2A and represented the most frequent subset in the NK cell repertoire. In contrast, minority CD57<sup>+</sup> or/and KIR<sup>+</sup> NK cell subsets were more efficient against AML. Overall, our data may help to optimize the selection of hematopoietic stem cell donors on the basis of immunogenetic KIR/HLA for ALL patients and identify the best NK cell candidates in immunotherapy for AML. |
| first_indexed | 2024-03-10T18:26:17Z |
| format | Article |
| id | doaj.art-9be1864094e8485a99503e9ab7abadb5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:26:17Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9be1864094e8485a99503e9ab7abadb52023-11-20T06:59:46ZengMDPI AGCancers2072-66942020-07-01127192710.3390/cancers12071927Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute LeukemiaDhon Roméo Makanga0Francesca Da Rin de Lorenzo1Gaëlle David2Catherine Willem3Léa Dubreuil4Nolwenn Legrand5Thierry Guillaume6Pierre Peterlin7Amandine Lebourgeois8Marie Christine Béné9Alice Garnier10Patrice Chevallier11Ketevan Gendzekhadze12Anne Cesbron13Katia Gagne14Béatrice Clemenceau15Christelle Retière16Etablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceUniversité de Nantes, INSERM U1232 CNRS, CRCINA, F-44000 Nantes, FranceHematology Clinic, CHU, 44000 Nantes, FranceHematology Clinic, CHU, 44000 Nantes, FranceUniversité de Nantes, INSERM U1232 CNRS, CRCINA, F-44000 Nantes, FranceHematology Clinic, CHU, 44000 Nantes, FranceUniversité de Nantes, INSERM U1232 CNRS, CRCINA, F-44000 Nantes, FranceHLA Laboratory, Department of Hematology and HCT, City of Hope, Medical Center, Duarte, CA 91010, USAEtablissement Français du Sang, 44011 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceUniversité de Nantes, INSERM U1232 CNRS, CRCINA, F-44000 Nantes, FranceEtablissement Français du Sang, 44011 Nantes, FranceNatural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-leukemic potential of NK cell subsets, taking into account these genetic parameters and cytomegalovirus (CMV) status. Hierarchical clustering analysis of NK cell subsets based on NKG2A, KIR, CD57 and NKG2C markers from 68 blood donors identified donor clusters characterized by a specific phenotypic NK cell repertoire linked to a particular immunogenetic KIR and HLA profile and CMV status. On the functional side, acute lymphoblastic leukemia (ALL) was better recognized by NK cells than acute myeloid leukemia (AML). However, a broad inter-individual disparity of NK cell responses exists against the same leukemic target, highlighting bad and good NK responders. The most effective NK cell subsets against different ALLs expressed NKG2A and represented the most frequent subset in the NK cell repertoire. In contrast, minority CD57<sup>+</sup> or/and KIR<sup>+</sup> NK cell subsets were more efficient against AML. Overall, our data may help to optimize the selection of hematopoietic stem cell donors on the basis of immunogenetic KIR/HLA for ALL patients and identify the best NK cell candidates in immunotherapy for AML.https://www.mdpi.com/2072-6694/12/7/1927KIRHLAnatural killer cellsrepertoireacute leukemiaCMV |
| spellingShingle | Dhon Roméo Makanga Francesca Da Rin de Lorenzo Gaëlle David Catherine Willem Léa Dubreuil Nolwenn Legrand Thierry Guillaume Pierre Peterlin Amandine Lebourgeois Marie Christine Béné Alice Garnier Patrice Chevallier Ketevan Gendzekhadze Anne Cesbron Katia Gagne Béatrice Clemenceau Christelle Retière Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia Cancers KIR HLA natural killer cells repertoire acute leukemia CMV |
| title | Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia |
| title_full | Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia |
| title_fullStr | Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia |
| title_full_unstemmed | Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia |
| title_short | Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia |
| title_sort | genetic and molecular basis of heterogeneous nk cell responses against acute leukemia |
| topic | KIR HLA natural killer cells repertoire acute leukemia CMV |
| url | https://www.mdpi.com/2072-6694/12/7/1927 |
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