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Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression

Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune...

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Autores principales: Kosmaczewska, Agata, Bocko, Dorota, Ciszak, Lidia, Wlodarska-Polinska, Iwona, Kornafel, Jan, Szteblich, Aleksandra, Masternak, Anna, Frydecka, Irena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313031/
https://www.ncbi.nlm.nih.gov/pubmed/22094905
http://dx.doi.org/10.1007/s12253-011-9471-y
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author Kosmaczewska, Agata
Bocko, Dorota
Ciszak, Lidia
Wlodarska-Polinska, Iwona
Kornafel, Jan
Szteblich, Aleksandra
Masternak, Anna
Frydecka, Irena
author_facet Kosmaczewska, Agata
Bocko, Dorota
Ciszak, Lidia
Wlodarska-Polinska, Iwona
Kornafel, Jan
Szteblich, Aleksandra
Masternak, Anna
Frydecka, Irena
author_sort Kosmaczewska, Agata
collection PubMed
description Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.
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spelling pubmed-33130312012-03-30 Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression Kosmaczewska, Agata Bocko, Dorota Ciszak, Lidia Wlodarska-Polinska, Iwona Kornafel, Jan Szteblich, Aleksandra Masternak, Anna Frydecka, Irena Pathol Oncol Res Research Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression. Springer Netherlands 2011-11-19 2012 /pmc/articles/PMC3313031/ /pubmed/22094905 http://dx.doi.org/10.1007/s12253-011-9471-y Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Research
Kosmaczewska, Agata
Bocko, Dorota
Ciszak, Lidia
Wlodarska-Polinska, Iwona
Kornafel, Jan
Szteblich, Aleksandra
Masternak, Anna
Frydecka, Irena
Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title_full Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title_fullStr Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title_full_unstemmed Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title_short Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression
title_sort dysregulated expression of both the costimulatory cd28 and inhibitory ctla-4 molecules in pb t cells of advanced cervical cancer patients suggests systemic immunosuppression related to disease progression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313031/
https://www.ncbi.nlm.nih.gov/pubmed/22094905
http://dx.doi.org/10.1007/s12253-011-9471-y
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