{"entity": "researcher", "timestamp": "2026-08-20T20:57:36.633Z", "family": "Kanaya", "given": "Minoru", "initials": "M", "orcid": "0000-0002-0035-8657", "affiliations": ["Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital and University of Oslo, Oslo, Norway."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/035eb746532c4679a1d85116dfd75d98.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/035eb746532c4679a1d85116dfd75d98"}}, "publications": [{"entity": "publication", "iuid": "9be7cc03b2c44b2eae7610a760cb73f4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9be7cc03b2c44b2eae7610a760cb73f4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9be7cc03b2c44b2eae7610a760cb73f4"}}, "title": "Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.", "authors": [{"family": "Philippon", "given": "Camille", "initials": "C"}, {"family": "Tao", "given": "Sudan", "initials": "S"}, {"family": "Clement", "given": "Dennis", "initials": "D"}, {"family": "Haroun-Izquierdo", "given": "Alvaro", "initials": "A", "orcid": "0000-0003-4557-3606", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ce9327b5d1b4c3f9fc91fd289cea6a8.json"}}, {"family": "Kichula", "given": "Katherine M", "initials": "KM", "orcid": "0000-0002-9817-3043", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/72b325af2be24f73b2343a0f6c3c87a6.json"}}, {"family": "Netskar", "given": "Herman", "initials": "H", "orcid": "0000-0002-3081-9581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dd8d11bf80a400ea9b92a8fa0c1b2d6.json"}}, {"family": "Brandt", "given": "Ludwig", "initials": "L", "orcid": "0000-0003-2040-3176", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/328e28faa0794e95a4e6cd96e2508ad0.json"}}, {"family": "Oei", "given": "Vincent Sheng", "initials": "VS", "orcid": "0000-0002-9336-529X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1b56943879714e6d9483c306ddb7587a.json"}}, {"family": "Kanaya", "given": "Minoru", "initials": "M", "orcid": "0000-0002-0035-8657", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/035eb746532c4679a1d85116dfd75d98.json"}}, {"family": "Lanuza", "given": "Pilar Maria", "initials": "PM"}, {"family": "Schaffer", "given": "Marie", "initials": "M"}, {"family": "Goodridge", "given": "Jodie P", "initials": "JP", "orcid": "0000-0001-7531-6032", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5adc441b4dd4567992da116d4faa53a.json"}}, {"family": "Horowitz", "given": "Amir", "initials": "A"}, {"family": "Zhu", "given": "Faming", "initials": "F", "orcid": "0000-0002-1963-9176", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c170188e089c420392583603a8af8c2d.json"}}, {"family": "Hammer", "given": "Quirin", "initials": "Q", "orcid": "0000-0003-2968-6061", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd1d59f056c149db98064ff1b0b99ed6.json"}}, {"family": "Sohlberg", "given": "Ebba", "initials": "E"}, {"family": "Majhi", "given": "Rakesh Kumar", "initials": "RK"}, {"family": "Kveberg", "given": "Lise", "initials": "L", "orcid": "0000-0001-9308-0641", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65d8133f4b424945b42e3dee2f4c2493.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Norman", "given": "Paul J", "initials": "PJ"}, {"family": "Malmberg", "given": "Karl-Johan", "initials": "KJ", "orcid": "0000-0002-8718-9373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553.json"}}], "type": "journal article", "published": "2023-08-22", "journal": {"title": "Blood Adv", "issn": "2473-9529", "volume": "7", "issue": "16", "pages": "4492-4504", "issn-l": null}, "abstract": "The functionality of natural killer (NK) cells is tuned during education and is associated with remodeling of the lysosomal compartment. We hypothesized that genetic variation in killer cell immunoglobulin-like receptor (KIR) and HLA, which is known to influence the functional strength of NK cells, fine-tunes the payload of effector molecules stored in secretory lysosomes. To address this possibility, we performed a high-resolution analysis of KIR and HLA class I genes in 365 blood donors and linked genotypes to granzyme B loading and functional phenotypes. We found that granzyme B levels varied across individuals but were stable over time in each individual and genetically determined by allelic variation in HLA class I genes. A broad mapping of surface receptors and lysosomal effector molecules revealed that DNAM-1 and granzyme B levels served as robust metric of the functional state in NK cells. Variation in granzyme B levels at rest was tightly linked to the lytic hit and downstream killing of major histocompatibility complex-deficient target cells. Together, these data provide insights into how variation in genetically hardwired receptor pairs tunes the releasable granzyme B pool in NK cells, resulting in predictable hierarchies in global NK cell function.", "doi": "10.1182/bloodadvances.2023009827", "pmid": "37327114", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10440473"}, {"db": "pii", "key": "496303"}], "notes": [], "created": "2026-08-20T12:18:49.188Z", "modified": "2026-08-20T12:18:49.482Z"}, {"entity": "publication", "iuid": "7f744718203e4e83be51df0b524bd916", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7f744718203e4e83be51df0b524bd916.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7f744718203e4e83be51df0b524bd916"}}, "title": "Adaptive single-KIR+NKG2C+ NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia.", "authors": [{"family": "Haroun-Izquierdo", "given": "Alvaro", "initials": "A", "orcid": "0000-0003-4557-3606", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ce9327b5d1b4c3f9fc91fd289cea6a8.json"}}, {"family": "Vincenti", "given": "Marianna", "initials": "M", "orcid": "0000-0001-5361-0185", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c9d5444f21804dd3b4d110839f5bd2dd.json"}}, {"family": "Netskar", "given": "Herman", "initials": "H", "orcid": "0000-0002-3081-9581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5dd8d11bf80a400ea9b92a8fa0c1b2d6.json"}}, {"family": "van Ooijen", "given": "Hanna", "initials": "H"}, {"family": "Zhang", "given": "Bin", "initials": "B"}, {"family": "Bendzick", "given": "Laura", "initials": "L"}, {"family": "Kanaya", "given": "Minoru", "initials": "M", "orcid": "0000-0002-0035-8657", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/035eb746532c4679a1d85116dfd75d98.json"}}, {"family": "Momayyezi", "given": "Pouria", "initials": "P"}, {"family": "Li", "given": "Shuo", "initials": "S"}, {"family": "Wiiger", "given": "Merete Thune", "initials": "MT"}, {"family": "Hoel", "given": "Hanna Julie", "initials": "HJ"}, {"family": "Krokeide", "given": "Silje Zandstra", "initials": "SZ"}, {"family": "Kremer", "given": "Veronika", "initials": "V"}, {"family": "Tjonnfjord", "given": "Geir", "initials": "G"}, {"family": "Berggren", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Wikstr\u00f6m", "given": "Kristina", "initials": "K"}, {"family": "Blomberg", "given": "Pontus", "initials": "P"}, {"family": "Alici", "given": "Evren", "initials": "E"}, {"family": "Felices", "given": "Martin", "initials": "M", "orcid": "0000-0002-5945-0634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7ec71e9866f6418ebae3b263e87411f5.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "H\u00f6glund", "given": "Petter", "initials": "P"}, {"family": "Valamehr", "given": "Bahram", "initials": "B"}, {"family": "Ljunggren", "given": "Hans-Gustaf", "initials": "HG"}, {"family": "Bj\u00f6rklund", "given": "Andreas", "initials": "A"}, {"family": "Hammer", "given": "Quirin", "initials": "Q"}, {"family": "Kveberg", "given": "Lise", "initials": "L", "orcid": "0000-0001-9308-0641", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65d8133f4b424945b42e3dee2f4c2493.json"}}, {"family": "Cichocki", "given": "Frank", "initials": "F"}, {"family": "Miller", "given": "Jeffrey S", "initials": "JS"}, {"family": "Malmberg", "given": "Karl-Johan", "initials": "KJ", "orcid": "0000-0002-8718-9373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553.json"}}, {"family": "Sohlberg", "given": "Ebba", "initials": "E", "orcid": "0000-0003-1942-0040", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4b5adb113a6642318b13759d58961c1b.json"}}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "J Immunother Cancer", "issn": "2051-1426", "volume": "10", "issue": "11", "issn-l": null}, "abstract": "Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)+NKG2C+ adaptive NK cells to maximize missing-self reactivity.\n\nWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.\n\nADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45dim blast subtypes.\n\nThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.", "doi": "10.1136/jitc-2022-005577", "pmid": "36319065", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9628692"}, {"db": "pii", "key": "jitc-2022-005577"}], "notes": [], "created": "2026-08-20T12:02:18.935Z", "modified": "2026-08-20T12:02:19.276Z"}]}