https://hdl.handle.net/2072/378100 2026-04-04T14:34:08Z https://hdl.handle.net/11351/14365 Footprints of Worldwide Adaptation in Structured Populations of Drosophila melanogaster Through the Expanded DEST 2.0 Genomic Resource Nunez, Joaquin; Coronado-Zamora, Marta; gautier, mathieu; Kapun, Martin; Steindl, Sonja; Ometto, Lino; Puerma, Eva Drosophila melanogaster; Dataset; Ecological genomics; Drosophila melanogaster; Conjunt de dades; Genòmica ecològica; Drosophila melanogaster; Conjunto de datos; Genómica ecológica; Large-scale genomic resources can place genetic variation into an ecologically informed context. To advance our understanding of the population genetics of the fruit fly Drosophila melanogaster, we present an expanded release of the community-generated population genomics resource Drosophila Evolution over Space and Time (DEST 2.0; https://dest.bio/). This release includes 530 high-quality pooled libraries from flies collected across six continents over more than a decade (2009 to 2021), most at multiple time points per year; 211 of these libraries are sequenced and shared here for the first time. We used this enhanced resource to elucidate several aspects of the species' demographic history and identify novel signs of adaptation across spatial and temporal dimensions. For example, we showed that the spatial genetic structure of populations is stable over time, but that drift due to seasonal contractions of population size causes populations to diverge over time. We identified signals of adaptation that vary between continents in genomic regions associated with xenobiotic resistance, consistent with independent adaptation to common pesticides. Moreover, by analyzing samples collected during spring and fall across Europe, we provide new evidence for seasonal adaptation related to loci associated with pathogen response. Furthermore, we have also released an updated version of the DEST genome browser. This is a useful tool for studying spatiotemporal patterns of genetic variation in this classic model system.; J.C.B.N. was supported by start-up funds from the University of Vermont. M.Kap. was supported by the Horizon Europe project FAIRiCUBE (grant #101059238). S.S. was supported by the Horizon Europe project FAIRiCUBE (grant #101059238). D.A.P. was supported by the NIH 2R35GM11816506 (MIRA grant). T.F. was supported by the Swiss National Science Foundation (SNSF) grants 31003A-182262, 310030_219283, and FZEB-0-214654. A.O.B. was supported by the National Institutes of Health R35 GM119686 and National Science Foundation CAREER #2145688 grants. J.G. was supported by grant PID2020-115874GB-I00 funded by MICIU/AEI /10.13039/501100011033, grant PID2023-148838NB-I00 funded by MICIU/AEI/10.13039/501100011033 and FEDER/EU, and grant 2021 SGR 00417 funded by the Departament de Recerca i Universitats, Generalitat de Catalunya. A.S.-G. was supported by the Ministerio de Ciencia e Innovación of Spain (MCIN/AEI/10.13039/501100011033; grant PID2020-113168GB-I00) and Comissió Interdepartamental de Recerca I Innovació Tecnològica of Catalonia, Spain (2021SGR00279). A.P. and M.T. were supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (NITRA), grant no. 451-03-66/2024-03/200007. A.B., M.P.G.G., and S.Casi. were supported by Ministerio de Ciencia e Innovación (PID2021-127107NB-I00) and AGAUR Generalitat de Catalunya (SGR 00526). C.S. was supported by the Austrian Science Funds, FWF, 10.55776/P32935, 10.55776/P33734. C.Fr. was supported by the German Research Foundation (DFG, grant # FR2973/11-1). D.O. was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/T007516/1. D.V. was supported by project QINV0196-IINV529010100 from the Pontificia Universidad Católica del Ecuador; Abbott was supported by VR-2015-04680 and VR-2020-05412. J.P. was supported by the Deutsche Forschungsgemeinschaft (DFG) projects 255619725 and 503272152. M.Kan. was supported by the Academy of Finland project 322980. M.S.V., M.J., and M.Ra. were supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (NITRA), grant no. 451-03-65/2024-03/ 200178. M.S.-R. was supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (NITRA) grant no. 451-03-47/2023-01/200178. M.G.R. was supported by Natural Environment Research Council (NERC), UK award NE/V001566/1. M.Re. was supported by the Bettencourt Schueller Foundation long-term partnership; this work was also partly supported by a CRI Core Research Fellowship. P.A.E. was supported by award #61-1673 from the Jane Coffin Childs Memorial Fund for Medical Research (www.jccfund.org). S.E.R.-O. was supported by PID2020-119255GB-I00 (MICINN, Spain), by the CERCA Programme/Generalitat de Catalunya and acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Programme for Centres of Excellence in R&D 2016–2019 and 2020–2023 (SEV-2015-0533, CEX2019-000917) and the European Regional Development Fund (ERDF). N.H. and C.L. were supported by Australian Research Council DP190102512. E.K. was supported by the European Molecular Biology Organization (EMBO) long-term fellowship ALT 248-02018. H.C. was supported by the French National Research Agency (ANR) project Drothermal (ANR-20-CE02-011-01). 2026-03-20T10:42:31Z https://hdl.handle.net/11351/14363 The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee Coukos, George; Donia, Marco; Gastman, Brian R; Goff, Stephanie; Harari, Alexandre; Gros, Alena Adoptive cell therapy; Immunotherapy; Tumor infiltrating lymphocyte; Terapia celular adoptiva; Inmunoterapia; Linfocitos infiltrantes de tumor; Teràpia cel·lular adoptiva; Immunoteràpia; Limfòcits infiltrants de tumor; Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in Europe. Here, we focus on early TIL studies in non-melanoma epithelial neoplasms. Increased understanding of cancer immunology has allowed changes in the TIL expansion process to include: (1) initial generation of TIL from fragments, (2) use of specialized large-scale culture vessels, (3) use of the rapid expansion protocol to enable ‘young’ TIL prosecution, and (4) treatment regimens employing non-myeloablative (NMA) chemotherapy followed by brief interleukin-2 administration. NMA leads to homeostatic proliferation of the transferred T cells, engraftment, profound neutropenia and lymphopenia, and improved clinical outcome. A key success of TIL ACT relies on the quality, specificity, and number of pre-existing TIL. This, in turn, is highly influenced by the suppressive tumor microenvironment. Thus, any means to alter ‘cold tumor (non-T cell inflamed)’ to ‘hot tumor (T cell inflamed)’ is theoretically desirable to improve both the quality and quantity of TIL obtained before harvest. Combinations of other immunotherapies such as application of ICB, co-stimulatory molecule agonist antibodies, autophagy inhibition, and dendritic cell support strategies could provide additional­ improvements in TIL therapy and enable harnessing of the adaptive immune response to enhance the clinical outcome of TIL-ACT patients. 2026-03-20T10:00:00Z https://hdl.handle.net/11351/14361 Specific Instability of HLA-A*03:01 Expression in HEK-293 Cells Area-Navarro, María; Pastor Moreno, Alba; Scholz Valero, Erika Margaret; Cerqueira, Américo; Tirado Herranz, Adrián; Marcilla, Miguel; Canals, Francesc HEK-293; HLA; Antigen presentation; HEK-293; HLA; Presentación de antígenos; HEK-293; HLA; Presentació d'antígens; HEK-293 is a highly transfectable human cell line widely used as a model for protein expression. Since large amounts of cells are often required for the purification of HLA immunopeptidomes, suspension-growing variants, such as HEK-293F, facilitate the generation of sufficient cell quantities. The HLA class I-typing of these cells is HLA-A*02:01, -A*03:01, -B*07:02, and -C*07:02. HEK-293T cells have been previously used as a source of HLA peptide ligands derived from SARS-CoV-2 proteins. In this study, we purified and analyzed the HLA-I immunopeptidome of HEK-293 and HEK-293F cells using mass spectrometry. Cell surface expression of specific HLA-I allotypes was determined using flow cytometry with allele-specific antibodies. The HLA-I immunopeptidome of HEK-293 cells contained ligands from all three HLA-I allotypes, whereas that of HEK-293F cells lacked peptides derived from HLA-A*03:01. Flow cytometry experiments confirmed the absence of HLA-A*03:01 expression on the surface of HEK-293F cells. Additionally, we generated a HEK-293 transfectant co-expressing the β5i proteasome subunit and the SARS-CoV-2 Spike protein. This transfectant showed selective loss of HLA-A*03:01 expression, suggesting that HEK-293 linages tend to specifically lose this allotype. We propose that HEK-293F cells are unsuitable for the identification of HLA-A*03:01 ligands or for stimulating T-cell responses restricted to this allele. Moreover, HLA-A*03:01 expression should be regularly monitored in HEK-293-derived cells.; This research was funded by Agència de Gestió d’Ajuts universitaris i de Recerca (AGAUR), grant number “2020PANDE00079” and Universitat Autònoma de Barcelona, grant number “PPC2024-38”. 2026-03-20T09:51:17Z https://hdl.handle.net/11351/14341 The barriers to uptake of artificial intelligence in hepatology and how to overcome them Clusmann, Jan; Bassegoda, Octavi; Seraphin, Tobias; Paintsil, Ellis Kobina; Balaguer-Montero, Maria; Schneider, Carolin V; Perez-Lopez, Raquel Inteligencia artificial; Consenso; Hepatología; Artificial intelligence; Consensus; Hepatology; Intel·ligència artificial; Consens; Hepatologia; Artificial intelligence (AI) methods in hepatology have proliferated since the mid-2010s, with numerous publications and some regulatory approvals. Yet, adoption of AI methods in real-world clinical practice and clinical research remains limited. Despite clear benefits of using AI to analyse complex data types in hepatology, such as histopathology, radiology images, multi-omics and more recently, natural language patient data, there are still substantial barriers and challenges to its integration into routine clinical workflows. In this position paper, we assess limitations and propose a set of clear recommendations aimed at both the development of AI systems and the broader hepatology environment to facilitate the transition of AI-based diagnostic, prognostic, and predictive tools into clinical care. In particular, we argue that the use of AI in clinical trials, seamless integration into hospital information systems and building AI literacy among clinicians will ultimately drive clinical adoption. We validate this perspective through a Delphi consensus involving 34 international experts from hepatology, AI, and data science, ensuring a comprehensive and consensus-driven evaluation of our recommendations.; JC is supported by the Mildred-Scheel-Postdoktorandenprogramm of the German Cancer Aid (grant #70115730). JNK is supported by the German Cancer Aid (DECADE, 70115166), the German Federal Ministry of Education and Research (PEARL, 01KD2104C; CAMINO, 01EO2101; TRANSFORM LIVER, 031L0312A; TANGERINE, 01KT2302 through ERA-NET Transcan; Come2Data, 16DKZ2044A; DEEP-HCC, 031L0315A; DECIPHER-M, 01KD2420A; NextBIG, 01ZU2402A), the German Academic Exchange Service (SECAI, 57616814), the German Federal Joint Committee (TransplantKI, 01VSF21048), the European Union’s Horizon Europe research and innovation programme (ODELIA, 101057091; GENIAL, 101096312), the European Research Council (ERC; NADIR, 101114631), the National Institutes of Health (EPICO, R01 CA263318) and the National Institute for Health and Care Research (NIHR, NIHR203331) Leeds Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This work was funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them. TL was funded by the German Cancer Aid (Deutsche Krebshilfe - DECADE 70115166), the Federal Ministry of Education and Research (BMBF - TRANSFORM LIVER 031L0312B) and the Federal Ministry of Health (BMG - DEEP LIVER 2520DAT111). C.V.S is supported by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (PTD 1-13/IA 532313), the Junior Principal Investigator Fellowship program of RWTH Aachen Excellence strategy and the NRW Rueckkehr Programme of the Ministry of Culture and Science of the German State of North Rhine-Westphalia, and the CRC 1382 project A11 and B09 funded by Deutsche Forschungsgesellschaft (DFG, German Research Foundation) – Project-ID 403224013 – SFB 1382“. 2026-03-16T12:58:23Z