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Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification

Despite the fact that management of EC is moving towards four TCGA-based molecular classifications, a pronounced variation in immune response among these molecular subtypes limits its clinical use. We aimed to investigate the determinant biomarker of ICI response in endometrial cancer (EC). We chara...

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Autores principales: Chen, Yi, You, Shuwen, Li, Jie, Zhang, Yifan, Kokaraki, Georgia, Epstein, Elisabeth, Carlson, Joseph, Huang, Wen-Kuan, Haglund, Felix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777298/
https://www.ncbi.nlm.nih.gov/pubmed/35069566
http://dx.doi.org/10.3389/fimmu.2021.788959
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author Chen, Yi
You, Shuwen
Li, Jie
Zhang, Yifan
Kokaraki, Georgia
Epstein, Elisabeth
Carlson, Joseph
Huang, Wen-Kuan
Haglund, Felix
author_facet Chen, Yi
You, Shuwen
Li, Jie
Zhang, Yifan
Kokaraki, Georgia
Epstein, Elisabeth
Carlson, Joseph
Huang, Wen-Kuan
Haglund, Felix
author_sort Chen, Yi
collection PubMed
description Despite the fact that management of EC is moving towards four TCGA-based molecular classifications, a pronounced variation in immune response among these molecular subtypes limits its clinical use. We aimed to investigate the determinant biomarker of ICI response in endometrial cancer (EC). We characterized transcriptome signatures associated with tumor immune microenvironment in EC. Two immune infiltration signatures were identified from the TCGA database (n = 520). The high- and low-infiltration clusters were compared for differences in patient clinical characteristics, genomic features, and immune cell transcription signatures for ICI prediction. A Lasso Cox regression model was applied to construct a prognostic gene signature. Time-dependent receiver operating characteristic curve, Kaplan–Meier curve, nomogram, and decision curve analyses were used to assess the prediction capacity. The efficacy of potential biomarker was validated by the Karolinska endometrial cancer cohort (n = 260). Immune signature profiling suggested that T follicular helper–like cells (Tfh) may be an important and favorable factor for EC; high Tfh infiltration showed potential for clinical use in the anti-PD-1 treatment. A Tfh Infiltration Risk Model (TIRM) established using eight genes was validated, and it outperformed the Immune Infiltration Risk Model. The TIRM had a stable prognostic value in combination with clinical risk factors and could be considered as a valuable tool in a clinical prediction model. We identified CRABP1 as an individual poor prognostic factor in EC. The Tfh-based classification distinguishes immune characteristics and predicts ICI efficacy. A nomogram based on Tfh-related risk score accurately predicted the prognosis of patients with EC, demonstrating superior performance to TCGA-based classification.
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spelling pubmed-87772982022-01-22 Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification Chen, Yi You, Shuwen Li, Jie Zhang, Yifan Kokaraki, Georgia Epstein, Elisabeth Carlson, Joseph Huang, Wen-Kuan Haglund, Felix Front Immunol Immunology Despite the fact that management of EC is moving towards four TCGA-based molecular classifications, a pronounced variation in immune response among these molecular subtypes limits its clinical use. We aimed to investigate the determinant biomarker of ICI response in endometrial cancer (EC). We characterized transcriptome signatures associated with tumor immune microenvironment in EC. Two immune infiltration signatures were identified from the TCGA database (n = 520). The high- and low-infiltration clusters were compared for differences in patient clinical characteristics, genomic features, and immune cell transcription signatures for ICI prediction. A Lasso Cox regression model was applied to construct a prognostic gene signature. Time-dependent receiver operating characteristic curve, Kaplan–Meier curve, nomogram, and decision curve analyses were used to assess the prediction capacity. The efficacy of potential biomarker was validated by the Karolinska endometrial cancer cohort (n = 260). Immune signature profiling suggested that T follicular helper–like cells (Tfh) may be an important and favorable factor for EC; high Tfh infiltration showed potential for clinical use in the anti-PD-1 treatment. A Tfh Infiltration Risk Model (TIRM) established using eight genes was validated, and it outperformed the Immune Infiltration Risk Model. The TIRM had a stable prognostic value in combination with clinical risk factors and could be considered as a valuable tool in a clinical prediction model. We identified CRABP1 as an individual poor prognostic factor in EC. The Tfh-based classification distinguishes immune characteristics and predicts ICI efficacy. A nomogram based on Tfh-related risk score accurately predicted the prognosis of patients with EC, demonstrating superior performance to TCGA-based classification. Frontiers Media S.A. 2022-01-07 /pmc/articles/PMC8777298/ /pubmed/35069566 http://dx.doi.org/10.3389/fimmu.2021.788959 Text en Copyright © 2022 Chen, You, Li, Zhang, Kokaraki, Epstein, Carlson, Huang and Haglund 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
Chen, Yi
You, Shuwen
Li, Jie
Zhang, Yifan
Kokaraki, Georgia
Epstein, Elisabeth
Carlson, Joseph
Huang, Wen-Kuan
Haglund, Felix
Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title_full Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title_fullStr Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title_full_unstemmed Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title_short Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification
title_sort follicular helper t-cell-based classification of endometrial cancer promotes precise checkpoint immunotherapy and provides prognostic stratification
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777298/
https://www.ncbi.nlm.nih.gov/pubmed/35069566
http://dx.doi.org/10.3389/fimmu.2021.788959
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