{"entity": "researcher", "timestamp": "2026-08-20T21:27:01.075Z", "family": "Malmberg", "given": "Karl-Johan", "initials": "KJ", "orcid": "0000-0002-8718-9373", "affiliations": ["Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.", "Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway.", "Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553"}}, "publications": [{"entity": "publication", "iuid": "2e468fb6ee84403d9cddc6c5ef0a7713", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2e468fb6ee84403d9cddc6c5ef0a7713.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2e468fb6ee84403d9cddc6c5ef0a7713"}}, "title": "Modulation of lytic molecules restrain serial killing in \u03b3\u03b4 T lymphocytes.", "authors": [{"family": "Sandoz", "given": "Patrick A", "initials": "PA", "orcid": "0000-0002-8379-7267", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d309ec0cb74f41a49a18e226079e6787.json"}}, {"family": "Kuhnigk", "given": "Kyra", "initials": "K", "orcid": "0000-0002-2265-8204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c9038f497daf47f4b001942f2d6a5788.json"}}, {"family": "Szabo", "given": "Edina K", "initials": "EK"}, {"family": "Thunberg", "given": "Sarah", "initials": "S", "orcid": "0000-0001-6912-6048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4c1a27ca8cd2429098eeb6bbebaa73f5.json"}}, {"family": "Erikson", "given": "Elina", "initials": "E"}, {"family": "Sandstr\u00f6m", "given": "Niklas", "initials": "N", "orcid": "0000-0001-6443-878X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b65278c9896e466f92f62f3ba1e58136.json"}}, {"family": "Verron", "given": "Quentin", "initials": "Q", "orcid": "0000-0001-5800-4379", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/31de7b29ad984949bc1901417bc7ed25.json"}}, {"family": "Brech", "given": "Andreas", "initials": "A"}, {"family": "Watzl", "given": "Carsten", "initials": "C", "orcid": "0000-0001-5195-0995", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/705dc690627d4843a59d21e3f2b62ea6.json"}}, {"family": "Wagner", "given": "Arnika K", "initials": "AK"}, {"family": "Alici", "given": "Evren", "initials": "E"}, {"family": "Malmberg", "given": "Karl-Johan", "initials": "KJ", "orcid": "0000-0002-8718-9373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553.json"}}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-5178-7593", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b4b8fcbedb54e2ba38633687f417ae8.json"}}], "type": "journal article", "published": "2023-09-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "6035", "issn-l": "2041-1723"}, "abstract": "\u03b3\u03b4 T cells play a pivotal role in protection against various types of infections and tumours, from early childhood on and throughout life. They consist of several subsets characterised by adaptive and innate-like functions, with V\u03b39V\u03b42 being the largest subset in human peripheral blood. Although these cells show signs of cytotoxicity, their modus operandi remains poorly understood. Here we explore, using live single-cell imaging, the cytotoxic functions of \u03b3\u03b4 T cells upon interactions with tumour target cells with high temporal and spatial resolution. While \u03b3\u03b4 T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by \u03b3\u03b4 T cells. Thus, our data provide new insights into the cytotoxic arsenal and functions of \u03b3\u03b4 T cells, which may guide the development of more efficient \u03b3\u03b4 T cell based adoptive immunotherapies.", "doi": "10.1038/s41467-023-41634-7", "pmid": "37758698", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10533871"}, {"db": "pii", "key": "10.1038/s41467-023-41634-7"}], "notes": [], "created": "2026-08-20T08:52:55.661Z", "modified": "2026-08-20T08:52:56.006Z"}, {"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": "9551a22f052a4e8eb02f43df52a2288c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9551a22f052a4e8eb02f43df52a2288c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9551a22f052a4e8eb02f43df52a2288c"}}, "title": "Modulation of lytic molecules restrain serial killing in \u03b3\u03b4 T lymphocytes", "authors": [{"family": "Onfelt", "given": "Bjorn", "initials": "B", "orcid": "0000-0001-5178-7593", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b4b8fcbedb54e2ba38633687f417ae8.json"}}, {"family": "Sandoz", "given": "Patrick", "initials": "P"}, {"family": "Kuhnigk", "given": "Kyra", "initials": "K"}, {"family": "Szabo", "given": "Edina", "initials": "E"}, {"family": "Thunberg", "given": "Sarah", "initials": "S", "orcid": "0000-0001-6912-6048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4c1a27ca8cd2429098eeb6bbebaa73f5.json"}}, {"family": "Erikson", "given": "Elina", "initials": "E"}, {"family": "Sandstr\u00f6m", "given": "Niklas", "initials": "N", "orcid": "0000-0001-6443-878X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b65278c9896e466f92f62f3ba1e58136.json"}}, {"family": "Verron", "given": "Quentin", "initials": "Q"}, {"family": "Brech", "given": "Andreas", "initials": "A"}, {"family": "Watzl", "given": "Carsten", "initials": "C", "orcid": "0000-0001-5195-0995", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/705dc690627d4843a59d21e3f2b62ea6.json"}}, {"family": "Wagner", "given": "Arnika", "initials": "A"}, {"family": "Alici", "given": "Evren", "initials": "E"}, {"family": "Malmberg", "given": "Karl Johan", "initials": "KJ", "orcid": "0000-0002-8718-9373", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e1b891c497ca402aaff79e8082f22553.json"}}, {"family": "Uhlin", "given": "Michael", "initials": "M", "orcid": "0000-0002-2177-6727", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/116cfe482bb941159ee2e7175f1cd095.json"}}], "type": "posted-content", "published": "2023-02-21", "journal": {"issn-l": null}, "abstract": null, "doi": "10.21203/rs.3.rs-2371463/v1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:58:48.009Z", "modified": "2026-08-20T12:58:48.055Z"}, {"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"}]}