{"entity": "researcher", "timestamp": "2026-07-12T09:04:35.220Z", "family": "Mangsbo", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-1355-2678", "affiliations": ["Department of Pharmaceutical Biosciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc"}}, "publications": [{"entity": "publication", "iuid": "192a4d6ad38642009586ef73e08341d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/192a4d6ad38642009586ef73e08341d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/192a4d6ad38642009586ef73e08341d5"}}, "title": "A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T proliferation and anti-tumor immunity in mice.", "authors": [{"family": "Mebrahtu", "given": "Aman", "initials": "A"}, {"family": "Laur\u00e9n", "given": "Ida", "initials": "I", "orcid": "0000-0003-0041-6084", "researcher": {"href": "https://publications.scilifelab.se/researcher/37ecae2143cf4534935defaca37e85ca.json"}}, {"family": "Veerman", "given": "Rosanne", "initials": "R"}, {"family": "Akpinar", "given": "G\u00f6zde G\u00fccl\u00fcler", "initials": "GG"}, {"family": "Lord", "given": "Martin", "initials": "M", "orcid": "0000-0002-3238-3187", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e14847c142f4c359f2d531601436897.json"}}, {"family": "Kostakis", "given": "Alexandros", "initials": "A", "orcid": "0009-0006-2252-2645", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd8822cc00c43788aaa88dc17f4b1e4.json"}}, {"family": "Astorga-Wells", "given": "Juan", "initials": "J", "orcid": "0000-0003-1017-8841", "researcher": {"href": "https://publications.scilifelab.se/researcher/14530d9aa03747858976b4889e959fe5.json"}}, {"family": "Dahllund", "given": "Leif", "initials": "L"}, {"family": "Olsson", "given": "Anders", "initials": "A"}, {"family": "Andersson", "given": "Oscar", "initials": "O"}, {"family": "Persson", "given": "Jonathan", "initials": "J"}, {"family": "Persson", "given": "Helena", "initials": "H"}, {"family": "D\u00f6nnes", "given": "Pierre", "initials": "P", "orcid": "0000-0002-4613-2952", "researcher": {"href": "https://publications.scilifelab.se/researcher/56d32d60f9b547be8096c448fc013246.json"}}, {"family": "Rockberg", "given": "Johan", "initials": "J"}, {"family": "Mangsbo", "given": "Sara", "initials": "S", "orcid": "0000-0002-1355-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}}], "type": "journal article", "published": "2024-11-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "9542", "issn-l": "2041-1723"}, "abstract": "Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity. In vivo, the selected bispecific antibody BiA9*2_HF loaded with peptide cargos induces improved antigen-specific proliferation of CD8+ (10-15 fold) and CD4+ T cells (2-7 fold) over control in draining lymph nodes. In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.", "doi": "10.1038/s41467-024-53839-5", "pmid": "39500897", "labels": {"Affinity Proteomics Uppsala": "Service", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11538452"}, {"db": "pii", "key": "10.1038/s41467-024-53839-5"}], "notes": [], "created": "2024-11-21T12:13:07.375Z", "modified": "2025-10-17T13:05:07.247Z"}, {"entity": "publication", "iuid": "d8c307b538944e43b439658ee0a24270", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d8c307b538944e43b439658ee0a24270.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d8c307b538944e43b439658ee0a24270"}}, "title": "Long-term SARS-CoV-2-specific and cross-reactive cellular immune responses correlate with humoral responses, disease severity, and symptomatology.", "authors": [{"family": "Laur\u00e9n", "given": "Ida", "initials": "I", "orcid": "0000-0003-0041-6084", "researcher": {"href": "https://publications.scilifelab.se/researcher/37ecae2143cf4534935defaca37e85ca.json"}}, {"family": "Havervall", "given": "Sebastian", "initials": "S"}, {"family": "Ng", "given": "Henry", "initials": "H", "orcid": "0000-0003-2873-9088", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fcb12c664a64724b5cd42a1267a5bea.json"}}, {"family": "Lord", "given": "Martin", "initials": "M"}, {"family": "Pettke", "given": "Aleksandra", "initials": "A"}, {"family": "Greilert-Norin", "given": "Nina", "initials": "N"}, {"family": "Gabrielsson", "given": "Lena", "initials": "L"}, {"family": "Chourlia", "given": "Aikaterini", "initials": "A"}, {"family": "Amo\u00eado-Leite", "given": "Catarina", "initials": "C"}, {"family": "Josyula", "given": "Vijay S", "initials": "VS"}, {"family": "Eltahir", "given": "Mohamed", "initials": "M"}, {"family": "Kerzeli", "given": "Iliana", "initials": "I"}, {"family": "Falk", "given": "August J", "initials": "AJ", "orcid": "0000-0002-7773-1851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6400bde68b46899515cef5bea05fca.json"}}, {"family": "Hober", "given": "Jonathan", "initials": "J"}, {"family": "Christ", "given": "Wanda", "initials": "W"}, {"family": "Wiberg", "given": "Anna", "initials": "A"}, {"family": "Hedhammar", "given": "My", "initials": "M"}, {"family": "Tegel", "given": "Hanna", "initials": "H"}, {"family": "Burman", "given": "Joachim", "initials": "J"}, {"family": "Xu", "given": "Feifei", "initials": "F"}, {"family": "Pin", "given": "Elisa", "initials": "E"}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J"}, {"family": "Christoffersson", "given": "Gustaf", "initials": "G"}, {"family": "Hober", "given": "Sophia", "initials": "S"}, {"family": "Nilsson", "given": "Peter", "initials": "P"}, {"family": "Philipson", "given": "Mia", "initials": "M"}, {"family": "D\u00f6nnes", "given": "Pierre", "initials": "P"}, {"family": "Lindsay", "given": "Robin", "initials": "R"}, {"family": "Th\u00e5lin", "given": "Charlotte", "initials": "C"}, {"family": "Mangsbo", "given": "Sara", "initials": "S", "orcid": "0000-0002-1355-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}}], "type": "journal article", "published": "2022-04-00", "journal": {"title": "Immun Inflamm Dis", "issn": "2050-4527", "volume": "10", "issue": "4", "pages": "e595", "issn-l": null}, "abstract": "Cellular immune memory responses post coronavirus disease 2019 (COVID-19) have been difficult to assess due to the risks of contaminating the immune response readout with memory responses stemming from previous exposure to endemic coronaviruses. The work herein presents a large-scale long-term follow-up study investigating the correlation between symptomology and cellular immune responses four to five months post seroconversion based on a unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific peptide pool that contains no overlapping peptides with endemic human coronaviruses.\n\nPeptide stimulated memory T cell responses were assessed with dual interferon-gamma (IFN\u03b3) and interleukin (IL)-2 Fluorospot. Serological analyses were performed using a multiplex antigen bead array.\n\nOur work demonstrates that long-term SARS-CoV-2-specific memory T cell responses feature dual IFN\u03b3 and IL-2 responses, whereas cross-reactive memory T cell responses primarily generate IFN\u03b3 in response to SARS-CoV-2 peptide stimulation. T cell responses correlated to long-term humoral immune responses. Disease severity as well as specific COVID-19 symptoms correlated with the magnitude of the SARS-CoV-2-specific memory T cell response four to five months post seroconversion.\n\nUsing a large cohort and a SARS-CoV-2-specific peptide pool we were able to substantiate that initial disease severity and symptoms correlate with the magnitude of the SARS-CoV-2-specific memory T cell responses.", "doi": "10.1002/iid3.595", "pmid": "35349756", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-03-31T06:07:11.524Z", "modified": "2022-03-31T06:07:11.636Z"}, {"entity": "publication", "iuid": "662e6300d57a45818e6a52bf43aa890a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/662e6300d57a45818e6a52bf43aa890a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/662e6300d57a45818e6a52bf43aa890a"}}, "title": "Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19.", "authors": [{"family": "Havervall", "given": "Sebastian", "initials": "S", "orcid": "0000-0003-1671-8183", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbd194b3cef64f9f9341fd163a035235.json"}}, {"family": "Ng", "given": "Henry", "initials": "H", "orcid": "0000-0003-2873-9088", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fcb12c664a64724b5cd42a1267a5bea.json"}}, {"family": "Jernbom Falk", "given": "August", "initials": "A", "orcid": "0000-0002-7773-1851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6400bde68b46899515cef5bea05fca.json"}}, {"family": "Greilert-Norin", "given": "Nina", "initials": "N", "orcid": "0000-0003-1492-9745", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0c03be884e4ae8840d0e0d04c411dd.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Marking", "given": "Ulrika", "initials": "U"}, {"family": "Laur\u00e9n", "given": "Ida", "initials": "I"}, {"family": "Gabrielsson", "given": "Lena", "initials": "L"}, {"family": "Salomonsson", "given": "Ann-Christin", "initials": "AC"}, {"family": "Aguilera", "given": "Katherina", "initials": "K"}, {"family": "Kihlgren", "given": "Martha", "initials": "M"}, {"family": "M\u00e5nsson", "given": "Maja", "initials": "M"}, {"family": "Rosell", "given": "Axel", "initials": "A", "orcid": "0000-0001-6280-0562", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcddaba7a96a406b994756ab71427baf.json"}}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-0880-5375", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbf3f75938f0442a9b1ae5c98565f44a.json"}}, {"family": "Andersson", "given": "Eni", "initials": "E"}, {"family": "Olofsson", "given": "Jennie", "initials": "J", "orcid": "0000-0002-8593-9089", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2b59febdeec4df99bf3a0d5480df305.json"}}, {"family": "Skoglund", "given": "Lovisa", "initials": "L"}, {"family": "Yousef", "given": "Jamil", "initials": "J", "orcid": "0000-0001-5915-1258", "researcher": {"href": "https://publications.scilifelab.se/researcher/86be17c932614797a876bb55c7ce566e.json"}}, {"family": "Pin", "given": "Elisa", "initials": "E", "orcid": "0000-0002-2158-2674", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccb4db02b9784587b62020716ab87247.json"}}, {"family": "Lord", "given": "Martin", "initials": "M", "orcid": "0000-0002-3238-3187", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e14847c142f4c359f2d531601436897.json"}}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M", "orcid": "0000-0002-7858-8233", "researcher": {"href": "https://publications.scilifelab.se/researcher/90fa86e9aeaa43ea9547e48b4f3f24e3.json"}}, {"family": "Hedhammar", "given": "My", "initials": "M"}, {"family": "Tegel", "given": "Hanna", "initials": "H"}, {"family": "D\u00f6nnes", "given": "Pierre", "initials": "P", "orcid": "0000-0002-4613-2952", "researcher": {"href": "https://publications.scilifelab.se/researcher/56d32d60f9b547be8096c448fc013246.json"}}, {"family": "Phillipson", "given": "Mia", "initials": "M", "orcid": "0000-0002-2387-0266", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebf9ffcab3e4a19add4c6dd51b727b1.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "Mangsbo", "given": "Sara", "initials": "S", "orcid": "0000-0002-1355-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}}, {"family": "Hober", "given": "Sophia", "initials": "S", "orcid": "0000-0003-0605-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8dd8ee4264d4e4b912dacad3106f40a.json"}}, {"family": "Th\u00e5lin", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-1345-6491", "researcher": {"href": "https://publications.scilifelab.se/researcher/130fb6ef6b774613a767e98f9f9b2eb4.json"}}], "type": "journal article", "published": "2022-01-00", "journal": {"title": "J. Intern. Med.", "issn": "1365-2796", "issn-l": "0954-6820", "volume": "291", "issue": "1", "pages": "72-80"}, "abstract": "Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.\n\nWe investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.\n\nAll COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).\n\nThe vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.", "doi": "10.1111/joim.13387", "pmid": "34459525", "labels": {"Autoimmunity and Serology Profiling": "Collaborative", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8661920"}], "notes": [], "created": "2021-08-31T10:38:04.811Z", "modified": "2022-12-02T10:46:29.165Z"}, {"entity": "publication", "iuid": "34832c01dbff4e7394549cc3c1f7bc36", "links": {"self": {"href": "https://publications.scilifelab.se/publication/34832c01dbff4e7394549cc3c1f7bc36.json"}, "display": {"href": "https://publications.scilifelab.se/publication/34832c01dbff4e7394549cc3c1f7bc36"}}, "title": "An evaluation of a FluoroSpot assay as a diagnostic tool to determine SARS-CoV-2 specific T cell responses.", "authors": [{"family": "Mangsbo", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-1355-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}}, {"family": "Havervall", "given": "Sebastian", "initials": "S"}, {"family": "Laur\u00e9n", "given": "Ida", "initials": "I"}, {"family": "Lindsay", "given": "Robin", "initials": "R", "orcid": "0000-0001-7867-8653", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0be8216b4c14ad4a02ef037a61a32b3.json"}}, {"family": "Jernbom Falk", "given": "August", "initials": "A", "orcid": "0000-0002-7773-1851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6400bde68b46899515cef5bea05fca.json"}}, {"family": "Marking", "given": "Ulrika", "initials": "U"}, {"family": "Lord", "given": "Martin", "initials": "M", "orcid": "0000-0002-3238-3187", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e14847c142f4c359f2d531601436897.json"}}, {"family": "Buggert", "given": "Marcus", "initials": "M"}, {"family": "D\u00f6nnes", "given": "Pierre", "initials": "P"}, {"family": "Christoffersson", "given": "Gustaf", "initials": "G"}, {"family": "Nilsson", "given": "Peter", "initials": "P"}, {"family": "Hober", "given": "Sophia", "initials": "S", "orcid": "0000-0003-0605-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8dd8ee4264d4e4b912dacad3106f40a.json"}}, {"family": "Phillipson", "given": "Mia", "initials": "M"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J"}, {"family": "Th\u00e5lin", "given": "Charlotte", "initials": "C"}], "type": "evaluation study", "published": "2021-09-30", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "16", "issue": "9", "pages": "e0258041", "issn-l": "1932-6203"}, "abstract": "Numerous assays evaluating serological and cellular responses have been developed to characterize immune responses against SARS-CoV-2. Serological assays are both cost- and time-effective compared to cellular assays, but cellular immune responses may provide a diagnostic value to determine previous SARS-CoV-2 infection in seronegative individuals. However, potential cross-reactive T cell responses stemming from prior encounters with human coronaviruses (HCoVs) may affect assay specificity. In this study, we evaluated the specificity and sensitivity of a SARS-CoV-2 IFN-\u03b3 Release Assay (IGRA) based on the FluoroSpot method employing commercially available SARS-CoV-2-specific peptide pools, as well as an in-house designed SARS-CoV-2 peptide pool restricted to 5 amino acid stretches or less aligning with endemic HCoVs. Blood samples were obtained from healthcare workers (HCW) 5-6 months post SARS-CoV-2 spike (S) IgG and nucleocapsid (N) IgG dual seroconversion (n = 187) and HCW who had been S IgG and N IgG dual seronegative at repeated occasions, including the current sampling time point (n = 102). In addition, samples were obtained 4 to 5 months post infection from 55 polymerase chain reaction (PCR)-confirmed COVID-19 patients. Assay specificity and sensitivity were calculated with serology as a reference standard for HCW. The in-house generated peptide pool displayed a specificity of 96.1%, while the commercially available peptide pools displayed specificities of 80.4% and 85.3%, respectively. Sensitivity was higher in a cohort of previously hospitalized COVID-19 patients (96.4% and 84.0% for the commercially available peptide pools and 92.7% for the in-house generated peptide pool) compared to the HCW cohort (92.0% and 66.8% for the commercially available peptide pools and 76.0% for the in-house generated peptide pool). Based on these findings, the individual diagnostic value of T cell immune responses against SARS-CoV-2 currently appears to be limited but remain an important research tool ahead.", "doi": "10.1371/journal.pone.0258041", "pmid": "34591918", "labels": {"Autoimmunity and Serology Profiling": "Technology development"}, "xrefs": [{"db": "pii", "key": "PONE-D-21-19070"}, {"db": "pmc", "key": "PMC8483319"}], "notes": [], "created": "2021-11-09T06:21:46.471Z", "modified": "2021-11-10T12:21:51.168Z"}, {"entity": "publication", "iuid": "8971713f42574a95affd0b83410a3a23", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8971713f42574a95affd0b83410a3a23.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8971713f42574a95affd0b83410a3a23"}}, "title": "Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations.", "authors": [{"family": "Kerzeli", "given": "Iliana K", "initials": "IK"}, {"family": "Lord", "given": "Martin", "initials": "M"}, {"family": "Doroszko", "given": "Milena", "initials": "M"}, {"family": "Elgendy", "given": "Ramy", "initials": "R", "orcid": "0000-0002-2592-3448", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a5ce4db4317446bb1ef113f7c6e8eb5.json"}}, {"family": "Chourlia", "given": "Aikaterini", "initials": "A"}, {"family": "Stepanek", "given": "Ivan", "initials": "I"}, {"family": "Larsson", "given": "Elinor", "initials": "E"}, {"family": "van Hooren", "given": "Luuk", "initials": "L"}, {"family": "Nelander", "given": "Sven", "initials": "S"}, {"family": "Malmstrom", "given": "Per-Uno", "initials": "PU"}, {"family": "Dragomir", "given": "Anca", "initials": "A"}, {"family": "Segersten", "given": "Ulrika", "initials": "U"}, {"family": "Mangsbo", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-1355-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c743bbcad6554f049c8fc5f64a6801bc.json"}}], "type": "journal article", "published": "2021-07-07", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "16", "issue": "7", "pages": "e0253178", "issn-l": "1932-6203"}, "abstract": "Bladder cancer, one of the most prevalent malignancies worldwide, remains hard to classify due to a staggering molecular complexity. Despite a plethora of diagnostic tools and therapies, it is hard to outline the key steps leading up to the transition from high-risk non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC). Carcinogen-induced murine models can recapitulate urothelial carcinogenesis and natural anti-tumor immunity. Herein, we have developed and profiled a novel model of progressive NMIBC based on 10 weeks of OH-BBN exposure in hepatocyte growth factor/cyclin dependent kinase 4 (R24C) (Hgf-Cdk4R24C) mice. The profiling of the model was performed by histology grading, single cell transcriptomic and proteomic analysis, while the derivation of a tumorigenic cell line was validated and used to assess in vivo anti-tumor effects in response to immunotherapy. Established NMIBC was present in females at 10 weeks post OH-BBN exposure while neoplasia was not as advanced in male mice, however all mice progressed to MIBC. Single cell RNA sequencing analysis revealed an intratumoral heterogeneity also described in the human disease trajectory. Moreover, although immune activation biomarkers were elevated in urine during carcinogen exposure, anti-programmed cell death protein 1 (anti-PD1) monotherapy did not prevent tumor progression. Furthermore, anti-PD1 immunotherapy did not control the growth of subcutaneous tumors formed by the newly derived urothelial cancer cell line. However, treatment with CpG-oligodeoxynucleotides (ODN) significantly decreased tumor volume, but only in females. In conclusion, the molecular map of this novel preclinical model of bladder cancer provides an opportunity to further investigate pharmacological therapies ahead with regards to both targeted drugs and immunotherapies to improve the strategies of how we should tackle the heterogeneous tumor microenvironment in urothelial bladder cancer to improve responses rates in the clinic.", "doi": "10.1371/journal.pone.0253178", "pmid": "34232958", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-39368"}, {"db": "pmc", "key": "PMC8262791"}], "notes": [], "created": "2021-12-07T21:40:24.842Z", "modified": "2021-12-10T15:10:01.474Z"}]}