Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context
Summary: Background: Natural killer (NK) cells have a unique capability of spontaneous cytotoxicity against malignant cells and hold promise for off-the-shelf cell therapy against cancer. One of the key challenges in the field is to improve NK cell homing to solid tumors. Methods: To gain a deeper...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423003778 |
| _version_ | 1797676648686944256 |
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| author | Mieszko Lachota Katarzyna Zielniok Daniel Palacios Minoru Kanaya Leena Peena Hanna Julie Hoel Merete Thune Wiiger Lise Kveberg Wojciech Hautz Radosław Zagożdżon Karl-Johan Malmberg |
| author_facet | Mieszko Lachota Katarzyna Zielniok Daniel Palacios Minoru Kanaya Leena Peena Hanna Julie Hoel Merete Thune Wiiger Lise Kveberg Wojciech Hautz Radosław Zagożdżon Karl-Johan Malmberg |
| author_sort | Mieszko Lachota |
| collection | DOAJ |
| description | Summary: Background: Natural killer (NK) cells have a unique capability of spontaneous cytotoxicity against malignant cells and hold promise for off-the-shelf cell therapy against cancer. One of the key challenges in the field is to improve NK cell homing to solid tumors. Methods: To gain a deeper understanding of the cellular mechanisms regulating trafficking of NK cells into the tumor, we used high-dimensional flow cytometry, mass cytometry, and single-cell RNA-sequencing combined with functional assays, creating a comprehensive map of human NK cell migration phenotypes. Findings: We found that the chemokine receptor repertoire of peripheral blood NK cells changes in a coordinated manner becoming progressively more diversified during NK cell differentiation and correlating tightly with the migratory response of the distinct NK cell subsets. Simultaneous ligation of CXCR1/2 and CX3CR1, synergistically potentiated the migratory response of NK cells. Analysis of 9471 solid cancers from publicly available TCGA/TARGET repositories revealed dominant chemokine patterns that varied across tumor types but with no tumor group expressing ligands for more than one chemokine receptor present on mature NK cells. Interpretation: The finding that chemokine stimulation can elicit a synergistic migratory response in NK cells combined with the identified lack of naturally occurring pairs of chemokines-chemokine receptors in human cancers may explain the systematic exclusion of NK cells from the tumor microenvironment and provides a basis for engineering next-generation NK cell therapies against malignancies. Funding: The Polish Ministry of Science and Higher Education, the National Science Centre, Poland, The Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, The Swedish Cancer Society, the Swedish Children's Cancer Foundation, The Swedish Research Council, The Center of Excellence: Precision Immunotherapy Alliance, Knut and Alice Wallenberg Foundation and National Cancer Institute. |
| first_indexed | 2024-03-11T22:32:19Z |
| format | Article |
| id | doaj.art-d7445aacf97a4d1dbabf8730cbfa6d79 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-11T22:32:19Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-d7445aacf97a4d1dbabf8730cbfa6d792023-09-23T05:11:17ZengElsevierEBioMedicine2352-39642023-10-0196104811Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in contextMieszko Lachota0Katarzyna Zielniok1Daniel Palacios2Minoru Kanaya3Leena Peena4Hanna Julie Hoel5Merete Thune Wiiger6Lise Kveberg7Wojciech Hautz8Radosław Zagożdżon9Karl-Johan Malmberg10Department of Clinical Immunology, Medical University of Warsaw, Warsaw, Poland; Department of Ophthalmology, Children’s Memorial Health Institute, Warsaw, PolandDepartment of Clinical Immunology, Medical University of Warsaw, Warsaw, PolandDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, NorwayDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, NorwayFinnish Red Cross Blood Service, Research and Development, Helsinki, FinlandDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, NorwayDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, NorwayDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, NorwayDepartment of Ophthalmology, Children’s Memorial Health Institute, Warsaw, PolandDepartment of Clinical Immunology, Medical University of Warsaw, Warsaw, PolandDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, Norway; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Corresponding author. Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, University of Oslo, Norway.Summary: Background: Natural killer (NK) cells have a unique capability of spontaneous cytotoxicity against malignant cells and hold promise for off-the-shelf cell therapy against cancer. One of the key challenges in the field is to improve NK cell homing to solid tumors. Methods: To gain a deeper understanding of the cellular mechanisms regulating trafficking of NK cells into the tumor, we used high-dimensional flow cytometry, mass cytometry, and single-cell RNA-sequencing combined with functional assays, creating a comprehensive map of human NK cell migration phenotypes. Findings: We found that the chemokine receptor repertoire of peripheral blood NK cells changes in a coordinated manner becoming progressively more diversified during NK cell differentiation and correlating tightly with the migratory response of the distinct NK cell subsets. Simultaneous ligation of CXCR1/2 and CX3CR1, synergistically potentiated the migratory response of NK cells. Analysis of 9471 solid cancers from publicly available TCGA/TARGET repositories revealed dominant chemokine patterns that varied across tumor types but with no tumor group expressing ligands for more than one chemokine receptor present on mature NK cells. Interpretation: The finding that chemokine stimulation can elicit a synergistic migratory response in NK cells combined with the identified lack of naturally occurring pairs of chemokines-chemokine receptors in human cancers may explain the systematic exclusion of NK cells from the tumor microenvironment and provides a basis for engineering next-generation NK cell therapies against malignancies. Funding: The Polish Ministry of Science and Higher Education, the National Science Centre, Poland, The Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, The Swedish Cancer Society, the Swedish Children's Cancer Foundation, The Swedish Research Council, The Center of Excellence: Precision Immunotherapy Alliance, Knut and Alice Wallenberg Foundation and National Cancer Institute.http://www.sciencedirect.com/science/article/pii/S2352396423003778NK cellsNatural killer cellsCancerImmunologyMigrationChemokine receptors |
| spellingShingle | Mieszko Lachota Katarzyna Zielniok Daniel Palacios Minoru Kanaya Leena Peena Hanna Julie Hoel Merete Thune Wiiger Lise Kveberg Wojciech Hautz Radosław Zagożdżon Karl-Johan Malmberg Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context EBioMedicine NK cells Natural killer cells Cancer Immunology Migration Chemokine receptors |
| title | Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context |
| title_full | Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context |
| title_fullStr | Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context |
| title_full_unstemmed | Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context |
| title_short | Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligationResearch in context |
| title_sort | mapping the chemotactic landscape in nk cells reveals subset specific synergistic migratory responses to dual chemokine receptor ligationresearch in context |
| topic | NK cells Natural killer cells Cancer Immunology Migration Chemokine receptors |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423003778 |
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