{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T04:19:05Z","timestamp":1766290745147,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"European Regional Development Fund (ERDF)","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"PHD scholarship by FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT through the ESF","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440","UIDB\/04539\/2020","UIDP\/04539\/2020","2023.02511.BD","SFRH\/BD\/148007\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered \u201ccold\u201d tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFN\u03b3 production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFN\u03b3 production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFN\u03b3 production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype.<\/jats:p>","DOI":"10.3390\/cancers17152508","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:37:23Z","timestamp":1753861043000},"page":"2508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive Receptor Repertoire and Functional Analysis of Peripheral NK Cells in Soft Tissue Sarcoma Patients"],"prefix":"10.3390","volume":"17","author":[{"given":"Luana Madalena","family":"Sousa","sequence":"first","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-0434","authenticated-orcid":false,"given":"Jani-Sofia","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Institute of Immunology, Faculty of Medicine (FMUC), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"given":"T\u00e2nia","family":"Fortes-Andrade","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Patr\u00edcia","family":"Couceiro","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"given":"Joana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Tumor Unit of the Locomotor Apparatus (UTAL), Orthopedics Service, University Clinic of Orthopedics, Coimbra Local Health Unit (ULSC), 3000-075 Coimbra, Portugal"}]},{"given":"R\u00faben","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Tumor Unit of the Locomotor Apparatus (UTAL), Orthopedics Service, University Clinic of Orthopedics, Coimbra Local Health Unit (ULSC), 3000-075 Coimbra, Portugal"}]},{"given":"Manuel","family":"Santos-Rosa","sequence":"additional","affiliation":[{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Institute of Immunology, Faculty of Medicine (FMUC), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7832-4134","authenticated-orcid":false,"given":"Paulo","family":"Freitas-Tavares","sequence":"additional","affiliation":[{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Tumor Unit of the Locomotor Apparatus (UTAL), Orthopedics Service, University Clinic of Orthopedics, Coimbra Local Health Unit (ULSC), 3000-075 Coimbra, Portugal"}]},{"given":"Jos\u00e9 Manuel","family":"Casanova","sequence":"additional","affiliation":[{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Tumor Unit of the Locomotor Apparatus (UTAL), Orthopedics Service, University Clinic of Orthopedics, Coimbra Local Health Unit (ULSC), 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7519-1620","authenticated-orcid":false,"given":"Paulo","family":"Rodrigues-Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Institute of Immunology, Faculty of Medicine (FMUC), University of Coimbra, 3000-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Centre of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1517\/13543784.2015.1076792","article-title":"Targeted Therapy and Promising Novel Agents for the Treatment of Advanced Soft Tissue Sarcomas","volume":"24","author":"Mohindra","year":"2015","journal-title":"Expert Opin. 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