{"entity": "researcher", "timestamp": "2026-07-20T12:55:47.109Z", "family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331"}}, "publications": [{"entity": "publication", "iuid": "324dda2cc5954036b5b3c062e03f2b62", "links": {"self": {"href": "https://publications.scilifelab.se/publication/324dda2cc5954036b5b3c062e03f2b62.json"}, "display": {"href": "https://publications.scilifelab.se/publication/324dda2cc5954036b5b3c062e03f2b62"}}, "title": "Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases", "authors": [{"family": "Karlsson", "given": "Joakim", "initials": "J"}, {"family": "Sah", "given": "Vasu R.", "initials": "VR"}, {"family": "Olofsson", "given": "Roger", "initials": "R"}, {"family": "Iqbal", "given": "BaggeMunir", "initials": "B"}, {"family": "Als\u00e9n", "given": "Samuel", "initials": "S"}, {"family": "Stenqvist", "given": "Sofia", "initials": "S"}, {"family": "Saxena", "given": "Alka", "initials": "A", "orcid": "0000-0002-1185-8649", "researcher": {"href": "https://publications.scilifelab.se/researcher/d230e0159adc4d7dbd1c3e7ded94dcec.json"}}, {"family": "Ny", "given": "Lars", "initials": "L"}, {"family": "Nilsson", "given": "Lisa M.", "initials": "LM"}, {"family": "Nilsson", "given": "Jonas A.", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}], "type": null, "published": "2023-11-16", "journal": {"title": "eLife", "issn": "2050-084X", "issn-l": "2050-084X", "volume": null, "issue": null, "pages": null}, "abstract": "Uveal melanoma (UM) is a rare melanoma originating in the eye\u2019s uvea, with 50% of patients experiencing metastasis predominantly in the liver. In contrast to cutaneous melanoma, there is only a limited effectiveness of combined immune checkpoint therapies, and half of patients succumb to recurrent disease after two years. This study aimed to provide a path towards enhancing immunotherapy efficacy by identifying and functionally validating tumor-reactive T cells in liver metastases of patients with UM. We employed single-cell RNA sequencing of biopsies and tumor-infiltrating lymphocytes (TILs) to identify potential tumor-reactive T cells. Patient-derived xenograft (PDX) models of UM metastases were created from patients, and tumor sphere cultures were generated from these models for co-culture with autologous or MART1-specific HLA-matched allogenic TILs. Activated T cells were subjected to TCR sequencing, and the TCRs were matched to those found in single-cell sequencing data from biopsies and expanded TILs. Our findings revealed that tumor-reactive T cells resided not only among activated and exhausted subsets of T cells, but also in a subset of cytotoxic effector cells. In conclusion, combining single-cell sequencing and functional analysis provides valuable insights into which T cells in UM may be useful for cell therapy amplification and marker selection.", "doi": null, "pmid": null, "labels": {"Spatial Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2023-11-21T09:05:31.204Z", "modified": "2025-12-01T07:37:45.626Z"}, {"entity": "publication", "iuid": "4317205fc07d449db7735d0732d85a4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4317205fc07d449db7735d0732d85a4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4317205fc07d449db7735d0732d85a4c"}}, "title": "Molecular profiling of driver events in metastatic uveal melanoma.", "authors": [{"family": "Karlsson", "given": "Joakim", "initials": "J", "orcid": "0000-0001-6332-4043", "researcher": {"href": "https://publications.scilifelab.se/researcher/6190c1a8a7d54cd6807f120e8748cfcd.json"}}, {"family": "Nilsson", "given": "Lisa M", "initials": "LM"}, {"family": "Mitra", "given": "Suman", "initials": "S"}, {"family": "Als\u00e9n", "given": "Samuel", "initials": "S"}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV", "orcid": "0000-0001-5883-8082", "researcher": {"href": "https://publications.scilifelab.se/researcher/beeaee610fe341d79fa92f2f4f9a9683.json"}}, {"family": "Sah", "given": "Vasu R", "initials": "VR"}, {"family": "Forsberg", "given": "Elin M V", "initials": "EMV", "orcid": "0000-0002-4196-3060", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e6342bc14ba426bbf61704b4873377a.json"}}, {"family": "Stierner", "given": "Ulrika", "initials": "U"}, {"family": "All-Eriksson", "given": "Charlotta", "initials": "C"}, {"family": "Einarsdottir", "given": "Berglind", "initials": "B"}, {"family": "Jespersen", "given": "Henrik", "initials": "H", "orcid": "0000-0002-6543-5369", "researcher": {"href": "https://publications.scilifelab.se/researcher/d220a3bcbfea44228722a123b25ec1b2.json"}}, {"family": "Ny", "given": "Lars", "initials": "L"}, {"family": "Lindn\u00e9r", "given": "Per", "initials": "P"}, {"family": "Larsson", "given": "Erik", "initials": "E"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R", "orcid": "0000-0001-5795-0355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1f8016d5e64418ca71f230e64e415ba.json"}}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}], "type": "journal article", "published": "2020-04-20", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "1894", "issn-l": "2041-1723"}, "abstract": "Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.", "doi": "10.1038/s41467-020-15606-0", "pmid": "32313009", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15606-0"}, {"db": "pmc", "key": "PMC7171146"}], "notes": [], "created": "2020-07-08T13:04:38.039Z", "modified": "2024-01-16T13:48:42.590Z"}, {"entity": "publication", "iuid": "675347d3c50d42f196d814d845d3b268", "links": {"self": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268.json"}, "display": {"href": "https://publications.scilifelab.se/publication/675347d3c50d42f196d814d845d3b268"}}, "title": "MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.", "authors": [{"family": "Gad", "given": "Helge", "initials": "H", "orcid": "0000-0001-6530-1443", "researcher": {"href": "https://publications.scilifelab.se/researcher/6273ef3dd1574185af0a83e9ab31bfe5.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "A", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Eshtad", "given": "Saeed", "initials": "S", "orcid": "0000-0001-6763-4700", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf4a705cae045feb64d1d9c7f8d9646.json"}}, {"family": "Jacques", "given": "Sylvain A", "initials": "SA"}, {"family": "Str\u00f6m", "given": "Cecilia E", "initials": "CE"}, {"family": "Svensson", "given": "Linda M", "initials": "LM"}, {"family": "Schultz", "given": "Niklas", "initials": "N"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Einarsdottir", "given": "Berglind Osk", "initials": "BO"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C", "orcid": "0000-0002-6272-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/9318cec5020f4c92b8393b20242c0d58.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications.scilifelab.se/researcher/47f7af2466c14275a42aad4a431b2dcb.json"}}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Berntsson", "given": "Ronnie P-A", "initials": "RP"}, {"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Jacques-Cordonnier", "given": "Marie-Caroline", "initials": "M"}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "A", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Olofsson", "given": "Roger", "initials": "R"}, {"family": "Johansson", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-5160-9543", "researcher": {"href": "https://publications.scilifelab.se/researcher/0667c14b327f44fd8a802acd9c3f1fb2.json"}}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Johansson", "given": "Lars", "initials": "L", "orcid": "0000-0001-7071-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9129e8ce7846e5b35b50f1ff4493e2.json"}}, {"family": "H\u00f6glund", "given": "Andreas", "initials": "A", "orcid": "0000-0002-1130-374X", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a484451caf40f2a1a196b36bb9c423.json"}}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Gaugaz", "given": "Fabienne Z", "initials": "FZ"}, {"family": "Vikingsson", "given": "Svante", "initials": "S"}, {"family": "Evers", "given": "Bastiaan", "initials": "B"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Wallner", "given": "Olov A", "initials": "OA"}, {"family": "Hammarstr\u00f6m", "given": "Lars G J", "initials": "LGJ"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Djureinovic", "given": "Tatjana", "initials": "T"}, {"family": "Puigvert", "given": "Jordi Carreras", "initials": "JC"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M", "orcid": "0000-0002-3857-1437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2b5f5d0486a4422b93a626a2cd1583f.json"}}, {"family": "Jeppsson", "given": "Fredrik", "initials": "F"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Lundin", "given": "Cecilia", "initials": "C"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Granelli", "given": "Ingrid", "initials": "I"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2014-04-10", "journal": {"volume": "508", "issn": "1476-4687", "issue": "7495", "pages": "215-221", "title": "Nature", "issn-l": "0028-0836"}, "abstract": "Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.", "doi": "10.1038/nature13181", "pmid": "24695224", "labels": {"Protein Science Facility (PSF)": null, "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "nature13181"}], "notes": "Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)\r\nADME of Therapeutics (UDOPP)\r\nBiochemical and Cellular Screening", "created": "2017-05-04T14:56:52.658Z", "modified": "2025-10-23T08:56:28.795Z"}]}