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Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

BACKGROUND: Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurre...

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Autores principales: Niu, Minli, Combs, Stephanie E., Linge, Annett, Krause, Mechthild, Baumann, Michael, Lohaus, Fabian, Ebert, Nadja, Tinhofer, Ingeborg, Budach, Volker, von der Grün, Jens, Rödel, Franz, Grosu, Anca-Ligia, Multhoff, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325802/
https://www.ncbi.nlm.nih.gov/pubmed/34332614
http://dx.doi.org/10.1186/s13014-021-01868-5
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author Niu, Minli
Combs, Stephanie E.
Linge, Annett
Krause, Mechthild
Baumann, Michael
Lohaus, Fabian
Ebert, Nadja
Tinhofer, Ingeborg
Budach, Volker
von der Grün, Jens
Rödel, Franz
Grosu, Anca-Ligia
Multhoff, Gabriele
author_facet Niu, Minli
Combs, Stephanie E.
Linge, Annett
Krause, Mechthild
Baumann, Michael
Lohaus, Fabian
Ebert, Nadja
Tinhofer, Ingeborg
Budach, Volker
von der Grün, Jens
Rödel, Franz
Grosu, Anca-Ligia
Multhoff, Gabriele
author_sort Niu, Minli
collection PubMed
description BACKGROUND: Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n = 23) and locoregional recurrent (n = 9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT. METHODS: EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20–30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n = 22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry. RESULTS: Patients with non-recurrent SCCHN had significantly lower proportions of CD19(+) B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3(+) T and CD3(+)/CD4(+) T helper cells continuously decreased between t0 and t3, whereas that of CD8(+) cytotoxic T cells and CD3(+)/CD56(+) NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4(+)/CD25(+)/FoxP3(+) regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4(+) T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56(+)/CD69(+), CD3(−)/CD56(+), CD3(−)/CD94(+), CD3(−)/NKG2D(+), CD3(−)/NKp30(+), CD3(−)/NKp46(+)) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregional recurrence, whereas in patients with locoregional recurrence, these subsets remained stably low until time of recurrence (t5). CONCLUSION: Monitoring the kinetics of lymphocyte subpopulations especially activatory NK cells before and after RCT might provide a clue with respect to the development of an early locoregional recurrence in patients with SCCHN. However, studies with larger patient cohorts are needed. TRIAL REGISTRATION: Observational Study on Biomarkers in Head and Neck Cancer (HNprädBio), NCT02059668. Registered on 11 February 2014, https://clinicaltrials.gov/ct2/show/NCT02059668. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01868-5.
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spelling pubmed-83258022021-08-02 Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) Niu, Minli Combs, Stephanie E. Linge, Annett Krause, Mechthild Baumann, Michael Lohaus, Fabian Ebert, Nadja Tinhofer, Ingeborg Budach, Volker von der Grün, Jens Rödel, Franz Grosu, Anca-Ligia Multhoff, Gabriele Radiat Oncol Research BACKGROUND: Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n = 23) and locoregional recurrent (n = 9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT. METHODS: EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20–30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n = 22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry. RESULTS: Patients with non-recurrent SCCHN had significantly lower proportions of CD19(+) B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3(+) T and CD3(+)/CD4(+) T helper cells continuously decreased between t0 and t3, whereas that of CD8(+) cytotoxic T cells and CD3(+)/CD56(+) NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4(+)/CD25(+)/FoxP3(+) regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4(+) T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56(+)/CD69(+), CD3(−)/CD56(+), CD3(−)/CD94(+), CD3(−)/NKG2D(+), CD3(−)/NKp30(+), CD3(−)/NKp46(+)) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregional recurrence, whereas in patients with locoregional recurrence, these subsets remained stably low until time of recurrence (t5). CONCLUSION: Monitoring the kinetics of lymphocyte subpopulations especially activatory NK cells before and after RCT might provide a clue with respect to the development of an early locoregional recurrence in patients with SCCHN. However, studies with larger patient cohorts are needed. TRIAL REGISTRATION: Observational Study on Biomarkers in Head and Neck Cancer (HNprädBio), NCT02059668. Registered on 11 February 2014, https://clinicaltrials.gov/ct2/show/NCT02059668. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01868-5. BioMed Central 2021-07-31 /pmc/articles/PMC8325802/ /pubmed/34332614 http://dx.doi.org/10.1186/s13014-021-01868-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Niu, Minli
Combs, Stephanie E.
Linge, Annett
Krause, Mechthild
Baumann, Michael
Lohaus, Fabian
Ebert, Nadja
Tinhofer, Ingeborg
Budach, Volker
von der Grün, Jens
Rödel, Franz
Grosu, Anca-Ligia
Multhoff, Gabriele
Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title_full Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title_fullStr Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title_full_unstemmed Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title_short Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
title_sort comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the german cancer consortium radiation oncology group (dktk-rog)
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325802/
https://www.ncbi.nlm.nih.gov/pubmed/34332614
http://dx.doi.org/10.1186/s13014-021-01868-5
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