ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context
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...
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doaj-b79954c108ec4188980fc8d2e8f675d42020-11-25T02:22:58ZengElsevierEBioMedicine2352-39642018-09-0135178188ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in contextXiang Hu0Ya-Qi Li1Qing-Guo Li2Yan-Lei Ma3Jun-Jie Peng4San-Jun Cai5Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authors at: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China.Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authors at: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China.Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authors at: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 20032, China.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. Keywords: ITGAE, Tumor-infiltrating lymphocytes, Colorectal cancer, Prognosishttp://www.sciencedirect.com/science/article/pii/S2352396418302913 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiang Hu Ya-Qi Li Qing-Guo Li Yan-Lei Ma Jun-Jie Peng San-Jun Cai |
spellingShingle |
Xiang Hu Ya-Qi Li Qing-Guo Li Yan-Lei Ma Jun-Jie Peng San-Jun Cai ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context EBioMedicine |
author_facet |
Xiang Hu Ya-Qi Li Qing-Guo Li Yan-Lei Ma Jun-Jie Peng San-Jun Cai |
author_sort |
Xiang Hu |
title |
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context |
title_short |
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context |
title_full |
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context |
title_fullStr |
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context |
title_full_unstemmed |
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal CancerResearch in context |
title_sort |
itgae defines cd8+ tumor-infiltrating lymphocytes predicting a better prognostic survival in colorectal cancerresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2018-09-01 |
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. Keywords: ITGAE, Tumor-infiltrating lymphocytes, Colorectal cancer, Prognosis |
url |
http://www.sciencedirect.com/science/article/pii/S2352396418302913 |
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