{"entity": "researcher", "timestamp": "2026-08-11T14:21:12.239Z", "family": "Hedenfalk", "given": "I", "initials": "I", "orcid": "0000-0002-6840-3397", "affiliations": ["Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.", "Lund University Cancer Centre (LUCC), Lund University, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8"}}, "publications": [{"entity": "publication", "iuid": "d4db29d93f3144d29d7dcb207e5ed083", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4db29d93f3144d29d7dcb207e5ed083.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4db29d93f3144d29d7dcb207e5ed083"}}, "title": "Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer.", "authors": [{"family": "Wang", "given": "Kang", "initials": "K", "orcid": "0000-0001-5401-1803", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bdb074014224910b0f34e893b15e660.json"}}, {"family": "Zerdes", "given": "Ioannis", "initials": "I", "orcid": "0000-0002-8304-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/f786763a4a0e4b5bb865ebb199eb6ca2.json"}}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ", "orcid": "0000-0003-4729-4205", "researcher": {"href": "https://publications.scilifelab.se/researcher/18aebf211fa640f48a7c8d860c168e5a.json"}}, {"family": "Sarhan", "given": "Dhifaf", "initials": "D", "orcid": "0000-0003-0196-4496", "researcher": {"href": "https://publications.scilifelab.se/researcher/22a235fbd46e49ba953ea339b8b8a507.json"}}, {"family": "Sun", "given": "Yizhe", "initials": "Y"}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Sifakis", "given": "Emmanouil G", "initials": "EG", "orcid": "0000-0001-9919-4471", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8506000a14a4a5286aa557ab67ef690.json"}}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Liu", "given": "Xingrong", "initials": "X"}, {"family": "Loman", "given": "Niklas", "initials": "N"}, {"family": "Hedenfalk", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-6840-3397", "researcher": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8.json"}}, {"family": "Bergh", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5526-1847", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd38f4f7704144ed9e3f869e197175e6.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0d4d98261f41268c76dd91345a1857.json"}}, {"family": "Hatschek", "given": "Thomas", "initials": "T"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Matikas", "given": "Alexios", "initials": "A", "orcid": "0000-0002-4122-9624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0af6483a77d746c2b838414692f1f4ed.json"}}, {"family": "Foukakis", "given": "Theodoros", "initials": "T", "orcid": "0000-0001-8952-9987", "researcher": {"href": "https://publications.scilifelab.se/researcher/7683c0280e9b4145aa54305fb08936a7.json"}}], "type": "journal article", "published": "2024-05-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3837", "issn-l": "2041-1723"}, "abstract": "Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.", "doi": "10.1038/s41467-024-47932-y", "pmid": "38714665", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11076527"}, {"db": "pii", "key": "10.1038/s41467-024-47932-y"}], "notes": [], "created": "2024-11-27T13:26:50.334Z", "modified": "2024-11-27T13:26:50.959Z"}, {"entity": "publication", "iuid": "d3faa64c950d41a3b247bdde8409ee7f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d3faa64c950d41a3b247bdde8409ee7f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d3faa64c950d41a3b247bdde8409ee7f"}}, "title": "Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma.", "authors": [{"family": "Linder", "given": "A", "initials": "A", "orcid": "0000-0002-9444-1346", "researcher": {"href": "https://publications.scilifelab.se/researcher/38b4f1c441ff49b891db4d7fb8163491.json"}}, {"family": "Westbom-Fremer", "given": "S", "initials": "S"}, {"family": "Mateoiu", "given": "C", "initials": "C"}, {"family": "Olsson Widjaja", "given": "A", "initials": "A"}, {"family": "\u00d6sterlund", "given": "T", "initials": "T", "orcid": "0000-0002-7870-8645", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd452c3f815846eba9a0da736ed6b252.json"}}, {"family": "Veerla", "given": "S", "initials": "S"}, {"family": "St\u00e5hlberg", "given": "A", "initials": "A"}, {"family": "Ulfenborg", "given": "B", "initials": "B", "orcid": "0000-0001-9242-4852", "researcher": {"href": "https://publications.scilifelab.se/researcher/a620033f4b57495885d66a5865d662d8.json"}}, {"family": "Hedenfalk", "given": "I", "initials": "I", "orcid": "0000-0002-6840-3397", "researcher": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8.json"}}, {"family": "Sundfeldt", "given": "K", "initials": "K", "orcid": "0000-0002-7135-3132", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb40cfcba9154502ad1d530c5e4a8a66.json"}}], "type": "journal article", "published": "2024-05-02", "journal": {"title": "Hum. Reprod.", "issn": "1460-2350", "volume": "39", "issue": "5", "pages": "1141-1154", "issn-l": "0268-1161"}, "abstract": "Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma?\n\nThe data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable.\n\nEndometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs).\n\nThe pathology biobanks of two university hospitals in Sweden were scrutinized to identify women with surgically removed endometrioma who subsequently developed ovarian carcinoma (1998-2016). Only 45 archival cases with EAOC and previous endometriosis were identified and after a careful pathology review, 25 cases were excluded due to reclassification into non-EAOC (n = 9) or because ovarian endometriosis could not be confirmed (n = 16). Further cases were excluded due to insufficient endometriosis tissue or poor DNA quality in either the endometriosis, carcinoma, or normal tissue (n = 9). Finally 11 cases had satisfactory DNA from all three locations and were eligible for further analysis.\n\nEpithelial cells were collected from formalin-fixed and paraffin-embedded (FFPE) sections by laser capture microdissection (endometrioma n = 11) or macrodissection (carcinoma n = 11) and DNA was extracted. Normal tissue from FFPE sections (n = 5) or blood samples collected at cancer diagnosis (n = 6) were used as the germline controls for each included patient. Whole-exome sequencing was performed (n = 33 samples). Somatic variants (single-nucleotide variants, indels, and copy number alterations) were characterized, and mutational signatures and kataegis were assessed. Microsatellite instability and mismatch repair status were confirmed with PCR and immunohistochemistry, respectively.\n\nThe median age for endometriosis surgery was 42 years, and 54 years for the subsequent ovarian carcinoma diagnosis. The median time between the endometriosis and ovarian carcinoma was 10 (7-30) years. The data showed that all paired samples harbored one or more shared somatic mutations. Non-silent mutations in cancer-associated genes were frequent in endometriosis; however, the same mutations were never observed in subsequent carcinomas. The degree of clonal dominance, demonstrated by variant allele frequency, showed a positive correlation with the time to cancer diagnosis (Spearman's rho 0.853, P < 0.001). Mutations in genes associated with immune escape were the most conserved between paired samples, and regions harboring these genes were frequently affected by copy number alterations in both sample types. Mutational burdens and mutation signatures suggested faulty DNA repair mechanisms in all cases.\n\nDatasets are available in the supplementary tables.\n\nEven though we located several thousands of surgically removed endometriomas between 1998 and 2016, only 45 paired samples were identified and even fewer, 11 cases, were eligible for sequencing. The observed high level of intra- and inter-heterogeneity in both groups (endometrioma and carcinoma) argues for further studies of the alleged genetic association.\n\nThe observation of shared somatic mutations in all paired samples supports a common cellular origin for ovarian endometriosis and ovarian carcinoma. However, contradicting previous conclusions, our data suggest that cancer-associated mutations in endometriosis years prior to the carcinoma were not directly associated with the malignant transformation. Rather, a resilient ovarian endometriosis may delay tumorigenesis. Furthermore, the data indicate that genetic alterations affecting the immune response are early and significant events.\n\nThe present work has been funded by the Sj\u00f6berg Foundation (2021-01145 to K.S.; 2022-01-11:4 to A.S.), Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (965552 to K.S.; 40615 to I.H.; 965065 to A.S.), Swedish Cancer Society (21-1848 to K.S.; 21-1684 to I.H.; 22-2080 to A.S.), BioCARE-A Strategic Research Area at Lund University (I.H. and S.W.-F.), Mrs Berta Kamprad's Cancer Foundation (FBKS-2019-28, I.H.), Cancer and Allergy Foundation (10381, I.H.), Region V\u00e4stra G\u00f6taland (A.S.), Sweden's Innovation Agency (2020-04141, A.S.), Swedish Research Council (2021-01008, A.S.), Roche in collaboration with the Swedish Society of Gynecological Oncology (S.W.-F.), Assar Gabrielsson Foundation (FB19-86, C.M.), and the Lena W\u00e4pplings Foundation (C.M.). A.S. declares stock ownership and is also a board member in Tulebovaasta, SiMSen Diagnostics, and Iscaff Pharma. A.S. has also received travel support from EMBL, Precision Medicine Forum, SLAS, and bioMCC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "doi": "10.1093/humrep/deae043", "pmid": "38459814", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11063555"}, {"db": "pii", "key": "7624782"}], "notes": [], "created": "2024-11-01T08:24:45.622Z", "modified": "2025-11-14T06:35:47.948Z"}, {"entity": "publication", "iuid": "675fb48cfa4a4d6b957ebee8caba3428", "links": {"self": {"href": "https://publications.scilifelab.se/publication/675fb48cfa4a4d6b957ebee8caba3428.json"}, "display": {"href": "https://publications.scilifelab.se/publication/675fb48cfa4a4d6b957ebee8caba3428"}}, "title": "Molecular patterns of resistance to immune checkpoint blockade in melanoma.", "authors": [{"family": "Lauss", "given": "Martin", "initials": "M"}, {"family": "Phung", "given": "Bengt", "initials": "B"}, {"family": "Borch", "given": "Troels Holz", "initials": "TH"}, {"family": "Harbst", "given": "Katja", "initials": "K", "orcid": "0000-0002-8225-1510", "researcher": {"href": "https://publications.scilifelab.se/researcher/daa5f87bad0d4e798c406854993eb7f0.json"}}, {"family": "Kaminska", "given": "Kamila", "initials": "K"}, {"family": "Ebbesson", "given": "Anna", "initials": "A"}, {"family": "Hedenfalk", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-6840-3397", "researcher": {"href": "https://publications.scilifelab.se/researcher/c852ed467120466f91d053425077c0b8.json"}}, {"family": "Yuan", "given": "Joan", "initials": "J"}, {"family": "Nielsen", "given": "Kari", "initials": "K", "orcid": "0000-0002-7363-0455", "researcher": {"href": "https://publications.scilifelab.se/researcher/202c6d3ce63340c4bbcca6dab9e320b1.json"}}, {"family": "Ingvar", "given": "Christian", "initials": "C"}, {"family": "Carneiro", "given": "Ana", "initials": "A"}, {"family": "Isaksson", "given": "Karolin", "initials": "K"}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications.scilifelab.se/researcher/5be0a3ec07654822a91df964eab1d6e4.json"}}, {"family": "Svane", "given": "Inge Marie", "initials": "IM", "orcid": "0000-0002-9451-6037", "researcher": {"href": "https://publications.scilifelab.se/researcher/c83b2b9332ba40fd90e1bce8eafa4c40.json"}}, {"family": "Donia", "given": "Marco", "initials": "M", "orcid": "0000-0003-4966-9752", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7f6af601067419786f6632b185f1fbe.json"}}, {"family": "J\u00f6nsson", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0001-6865-0147", "researcher": {"href": "https://publications.scilifelab.se/researcher/0099af8e34f64a37a35392d32a0d357e.json"}}], "type": "journal article", "published": "2024-04-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3075", "issn-l": "2041-1723"}, "abstract": "Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways are observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions have a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and T cell receptor (TCR) clonality analyses. One anti-PD1 resistant lesion harbors a distinct immune cell niche, however, anti-PD1 resistant tumors are generally immune poor with non-expanded TCR clones. Such immune poor microenvironments are associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors have reduced fractions of PD1+ CD8+ T cells as compared to ICB na\u00efve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.", "doi": "10.1038/s41467-024-47425-y", "pmid": "38594286", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11004175"}, {"db": "pii", "key": "10.1038/s41467-024-47425-y"}], "notes": [], "created": "2024-11-25T10:16:32.724Z", "modified": "2025-11-07T13:30:42.010Z"}]}