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PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer
BACKGROUND: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunothera...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393709/ https://www.ncbi.nlm.nih.gov/pubmed/36003382 http://dx.doi.org/10.3389/fimmu.2022.947841 |
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author | Dong, Hongmei Xie, Chaoyu Yao, Zhimeng Zhao, Ruijun Lin, Yusheng Luo, Yichen Chen, Shuanglong Qin, Yanfang Chen, Yexi Zhang, Hao |
author_facet | Dong, Hongmei Xie, Chaoyu Yao, Zhimeng Zhao, Ruijun Lin, Yusheng Luo, Yichen Chen, Shuanglong Qin, Yanfang Chen, Yexi Zhang, Hao |
author_sort | Dong, Hongmei |
collection | PubMed |
description | BACKGROUND: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. METHODS: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8(+) T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. RESULTS: High PTPRO expression was related to high infiltration levels of CD8(+) T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8(+) T cells in the TIME, we focused on the impact of PTPRO expression on CD8(+) T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). CONCLUSION: PTPRO significantly impacts CD8(+) T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients. |
format | Online Article Text |
id | pubmed-9393709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93937092022-08-23 PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer Dong, Hongmei Xie, Chaoyu Yao, Zhimeng Zhao, Ruijun Lin, Yusheng Luo, Yichen Chen, Shuanglong Qin, Yanfang Chen, Yexi Zhang, Hao Front Immunol Immunology BACKGROUND: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. METHODS: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8(+) T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. RESULTS: High PTPRO expression was related to high infiltration levels of CD8(+) T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8(+) T cells in the TIME, we focused on the impact of PTPRO expression on CD8(+) T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). CONCLUSION: PTPRO significantly impacts CD8(+) T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9393709/ /pubmed/36003382 http://dx.doi.org/10.3389/fimmu.2022.947841 Text en Copyright © 2022 Dong, Xie, Yao, Zhao, Lin, Luo, Chen, Qin, Chen and Zhang 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 Dong, Hongmei Xie, Chaoyu Yao, Zhimeng Zhao, Ruijun Lin, Yusheng Luo, Yichen Chen, Shuanglong Qin, Yanfang Chen, Yexi Zhang, Hao PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title | PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title_full | PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title_fullStr | PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title_full_unstemmed | PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title_short | PTPRO-related CD8(+) T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
title_sort | ptpro-related cd8(+) t-cell signatures predict prognosis and immunotherapy response in patients with breast cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393709/ https://www.ncbi.nlm.nih.gov/pubmed/36003382 http://dx.doi.org/10.3389/fimmu.2022.947841 |
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