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ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer
BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154785/ https://www.ncbi.nlm.nih.gov/pubmed/30100393 http://dx.doi.org/10.1016/j.ebiom.2018.08.003 |
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author | Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun |
author_facet | Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun |
author_sort | Hu, Xiang |
collection | PubMed |
description | BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of substantial benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes. METHODS: We investigated whether ITGAE could be used to discriminate reactive CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1 = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further phenotyping of ITGAE+ cells and the mechanistic basis were investigated. FINDINGS: In the training and testing sets from TCGA, ITGAE expression, which is strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently predicted longer disease-free survival (DFS) and overall survival (OS). In line with this, the association between ITGAE+ lymphocytes and survival has been confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the series always co-stained with CD8 were preferentially located in the tumor. Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial–mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. Finally, gene set enrichment analysis showed that immune activation was significantly enriched in the high ITGAE+ TIL group, accompanied by enriched EMT-related pathways. INTERPRETATION: Because of the specified expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for the rapid identification of immune infiltration in CRC. |
format | Online Article Text |
id | pubmed-6154785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-61547852018-09-26 ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun EBioMedicine Research paper BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of substantial benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes. METHODS: We investigated whether ITGAE could be used to discriminate reactive CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1 = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further phenotyping of ITGAE+ cells and the mechanistic basis were investigated. FINDINGS: In the training and testing sets from TCGA, ITGAE expression, which is strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently predicted longer disease-free survival (DFS) and overall survival (OS). In line with this, the association between ITGAE+ lymphocytes and survival has been confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the series always co-stained with CD8 were preferentially located in the tumor. Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial–mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. Finally, gene set enrichment analysis showed that immune activation was significantly enriched in the high ITGAE+ TIL group, accompanied by enriched EMT-related pathways. INTERPRETATION: Because of the specified expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for the rapid identification of immune infiltration in CRC. Elsevier 2018-08-09 /pmc/articles/PMC6154785/ /pubmed/30100393 http://dx.doi.org/10.1016/j.ebiom.2018.08.003 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Hu, Xiang Li, Ya-Qi Li, Qing-Guo Ma, Yan-Lei Peng, Jun-Jie Cai, San-Jun ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title | ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title_full | ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title_fullStr | ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title_full_unstemmed | ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title_short | ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer |
title_sort | itgae defines cd8+ tumor-infiltrating lymphocytes predicting a better prognostic survival in colorectal cancer |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154785/ https://www.ncbi.nlm.nih.gov/pubmed/30100393 http://dx.doi.org/10.1016/j.ebiom.2018.08.003 |
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