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Immune Adaptation of Colorectal Cancer Stem Cells and Their Interaction With the Tumor Microenvironment.

ABSTRACT: Metastasis is the primary cause of death in colorectal cancer (CRC) patients. Emerging evidence has shown that CRC stem cells (CRCSCs) play a significant role in metastatic dissemination and tumor recurrence. However, strategies for targeting CRCSCs are limited because CRCSCs are resistant to therapeutic interventions and because the tumor microenvironment (TME) provides a supportive niche. Moreover, growing evidence highlights the critical role of CRCSCs in immune adaptation and modulation of the TME. CRCSCs escape immune surveillance by avoiding recognition by the innate immune system and shaping the TME through exosomes, cytokines, and chemokines to generate an immunosuppressive niche that facilitates cancer progression. In this review, we summarize studies investigating the immunomodulatory properties of CRCSCs and their underlying mechanisms in order to improve the efficacy of treatment strategies against advanced CRC.

SUBMITTER: Lin CC

PROVIDER: S-EPMC7708331 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Immune Adaptation of Colorectal Cancer Stem Cells and Their Interaction With the Tumor Microenvironment.

Lin Chun-Chi CC Liao Tsai-Tsen TT Yang Muh-Hwa MH

Frontiers in oncology 20201118

Metastasis is the primary cause of death in colorectal cancer (CRC) patients. Emerging evidence has shown that CRC stem cells (CRCSCs) play a significant role in metastatic dissemination and tumor recurrence. However, strategies for targeting CRCSCs are limited because CRCSCs are resistant to therapeutic interventions and because the tumor microenvironment (TME) provides a supportive niche. Moreover, growing evidence highlights the critical role of CRCSCs in immune adaptation and modulation of t ...[more]

PMID: 33312953

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Project description:BackgroundThe tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).MethodsTranscriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.ResultsGene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717-0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.ConclusionsIn this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.

Dataset Information

Immune Adaptation of Colorectal Cancer Stem Cells and Their Interaction With the Tumor Microenvironment.

Publications

Immune Adaptation of Colorectal Cancer Stem Cells and Their Interaction With the Tumor Microenvironment.

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