{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T08:09:32Z","timestamp":1767773372146,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission\u2019s Horizon 2020 research and innovation program","award":["675132"],"award-info":[{"award-number":["675132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) represent major primary liver cancers, affecting one of the most vital organs in the human body. T regulatory (Treg) cells play an important role in liver cancers through the immunosuppression of antitumor immune responses. The current study focuses on the characterization of circulating natural killer (NK) cells and T cell subsets, including Treg cells, in CCA and HCC patients, before and after surgical tumor resection, in order to understand the effect of tumor resection on the homeostasis of peripheral blood NK cells and T cells. Methods: Whole blood assays were performed to monitor immune alterations and the functional competence of circulating lymphocytes in a group of ten healthy individuals, eight CCA patients, and twenty HCC patients, before and one month after the surgical procedure, using flow cytometry, cell sorting, and qRT-PCR. Results: Before tumor resection, both HCC and CCA patients display increased percentages of CD8+ Treg cells and decreased frequencies of circulating CD4+ Treg cells. Notwithstanding, no functional impairment was detected on circulating CD4+ Treg cells, neither in CCA nor in HCC patients. Interestingly, the frequency of peripheral CD4+ Treg cells increased from 0.55% \u00b1 0.49 and 0.71% \u00b1 0.54 (in CCA and HCC, respectively) at T0 to 0.99% \u00b1 0.91 and 1.17% \u00b1 0.33 (in CCA and HCC, respectively) at T1, following tumor resection. Conclusions: Our results suggest mechanisms of immune modulation induced by tumor resection.<\/jats:p>","DOI":"10.3390\/jcm13196011","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T07:39:52Z","timestamp":1728459592000},"page":"6011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tumor Resection in Hepatic Carcinomas Restores Circulating T Regulatory Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-1054","authenticated-orcid":false,"given":"Carmen","family":"Mart\u00edn-Sierra","sequence":"first","affiliation":[{"name":"Flow Cytometry Unit, Department of Clinical Pathology, Hospitais da Universidade de Coimbra, Unidade Local de Sa\u00fade de Coimbra, 3000-076 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"}]},{"given":"Ricardo","family":"Martins","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Unidade Transplanta\u00e7\u00e3o Hep\u00e1tica Pedi\u00e1trica e de Adultos, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Servi\u00e7o de Cirurgia Geral, Unidade HBP, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal"}]},{"given":"Margarida","family":"Coucelo","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Unidade Funcional de Hematologia Molecular, Servi\u00e7o de Hematologia Cl\u00ednica, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-7871","authenticated-orcid":false,"given":"Ana Margarida","family":"Abrantes","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-8059","authenticated-orcid":false,"given":"Rui","family":"Caetano Oliveira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal"},{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Jos\u00e9 Guilherme","family":"Tralh\u00e3o","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"Unidade Transplanta\u00e7\u00e3o Hep\u00e1tica Pedi\u00e1trica e de Adultos, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Servi\u00e7o de Cirurgia Geral, Unidade HBP, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria Filomena","family":"Botelho","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-548 Coimbra, Portugal"}]},{"given":"Emanuel","family":"Furtado","sequence":"additional","affiliation":[{"name":"Unidade Transplanta\u00e7\u00e3o Hep\u00e1tica Pedi\u00e1trica e de Adultos, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5357-3601","authenticated-orcid":false,"given":"Maria Ros\u00e1rio","family":"Domingues","sequence":"additional","affiliation":[{"name":"CESAM\u2014Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Mass Spectrometry Center, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Artur","family":"Paiva","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Department of Clinical Pathology, Hospitais da Universidade de Coimbra, Unidade Local de Sa\u00fade de Coimbra, 3000-076 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"Instituto Polit\u00e9cnico de Coimbra, ESTESC-Coimbra Health School, Ci\u00eancias Biom\u00e9dicas Laboratoriais, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-6118","authenticated-orcid":false,"given":"Paula","family":"Laranjeira","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Department of Clinical Pathology, Hospitais da Universidade de Coimbra, Unidade Local de Sa\u00fade de Coimbra, 3000-076 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Center of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-061 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/cmi.2016.4","article-title":"Adaptive Immunity in the Liver","volume":"13","author":"Shuai","year":"2016","journal-title":"Cell Mol. 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