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Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients

BACKGROUND: Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the...

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Autores principales: Knebel, Moritz, Körner, Sandrina, Kühn, Jan Philipp, Wemmert, Silke, Brust, Lukas, Smola, Sigrun, Wagner, Mathias, Bohle, Rainer M., Morris, Luc G. T., Pandey, Abhinav, Schick, Bernhard, Linxweiler, Maximilian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294051/
https://www.ncbi.nlm.nih.gov/pubmed/37383237
http://dx.doi.org/10.3389/fimmu.2023.1172768
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author Knebel, Moritz
Körner, Sandrina
Kühn, Jan Philipp
Wemmert, Silke
Brust, Lukas
Smola, Sigrun
Wagner, Mathias
Bohle, Rainer M.
Morris, Luc G. T.
Pandey, Abhinav
Schick, Bernhard
Linxweiler, Maximilian
author_facet Knebel, Moritz
Körner, Sandrina
Kühn, Jan Philipp
Wemmert, Silke
Brust, Lukas
Smola, Sigrun
Wagner, Mathias
Bohle, Rainer M.
Morris, Luc G. T.
Pandey, Abhinav
Schick, Bernhard
Linxweiler, Maximilian
author_sort Knebel, Moritz
collection PubMed
description BACKGROUND: Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells. METHODS: The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68. RESULTS: Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients’ overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome. CONCLUSION: Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies.
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spelling pubmed-102940512023-06-28 Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients Knebel, Moritz Körner, Sandrina Kühn, Jan Philipp Wemmert, Silke Brust, Lukas Smola, Sigrun Wagner, Mathias Bohle, Rainer M. Morris, Luc G. T. Pandey, Abhinav Schick, Bernhard Linxweiler, Maximilian Front Immunol Immunology BACKGROUND: Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells. METHODS: The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68. RESULTS: Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients’ overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome. CONCLUSION: Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies. Frontiers Media S.A. 2023-06-13 /pmc/articles/PMC10294051/ /pubmed/37383237 http://dx.doi.org/10.3389/fimmu.2023.1172768 Text en Copyright © 2023 Knebel, Körner, Kühn, Wemmert, Brust, Smola, Wagner, Bohle, Morris, Pandey, Schick and Linxweiler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Knebel, Moritz
Körner, Sandrina
Kühn, Jan Philipp
Wemmert, Silke
Brust, Lukas
Smola, Sigrun
Wagner, Mathias
Bohle, Rainer M.
Morris, Luc G. T.
Pandey, Abhinav
Schick, Bernhard
Linxweiler, Maximilian
Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title_full Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title_fullStr Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title_full_unstemmed Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title_short Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation on 101 patients
title_sort prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the tcga-hnsc cohort and immunohistochemical validation on 101 patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294051/
https://www.ncbi.nlm.nih.gov/pubmed/37383237
http://dx.doi.org/10.3389/fimmu.2023.1172768
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