ArticleEBioMedicine2018
ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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28 citing papers in PubMed, 51 citations in OpenAlex.
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- Tissue-resident memory T cells in gastrointestinal cancer immunology and immunotherapy: ready for prime time?Journal for immunotherapy of cancer · 2022Review
- An Overview of Tissue-Resident Memory T Cells in the Intestine: From Physiological Functions to Pathological Mechanisms.Frontiers in immunology · 2022Review
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Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-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.
methodsWe 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.
findingsIn 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.
interpretationBecause 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.
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