CCR7 as a therapeutic target in Cancer

Salem, A. R.; Alotaibi, Mashael Bin Alamir; Mroueh, Rima; Basheer, Haneen A.; Afarinkia, K.

doi:10.1016/j.bbcan.2020.188499

Cited by 67 publications

(53 citation statements)

References 270 publications

(298 reference statements)

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“…Finally, we recognized eight hub IRPGs strongly correlated with survival and immune-relevant biological processes. For instance, previous studies have shown that CCR7 was correlated with lymph node metastasis in patients with CC and was an excellent therapeutic target in cancer ( Dai et al, 2017 ; Salem et al, 2021 ). Moreover, it has been reported that high CD3E expression correlated with improved disease-specific survival in CC ( Punt et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

Shen

2021

Front. Genet.

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The cross-talk between tumor cells and the tumor microenvironment (TME) is an important factor in determining the tumorigenesis and progression of cervical cancer (CC). However, clarifying the potential mechanisms which trigger the above biological processes remains a challenge. The present study focused on immune-relevant differences at the transcriptome and somatic mutation levels through an integrative multi-omics analysis based on The Cancer Genome Atlas database. The objective of the study was to recognize the specific immune-related prognostic factors predicting the survival and response to immunotherapy of patients with CC. Firstly, eight hub immune-related prognostic genes were ultimately identified through construction of a protein–protein interaction network and Cox regression analysis. Secondly, 32 differentially mutated genes were simultaneously identified based on the different levels of immune infiltration. As a result, an immune gene-related prognostic model (IGRPM), including six factors (chemokine receptor 7 [CCR7], CD3d molecule [CD3D], CD3e molecule [CD3E], and integrin subunit beta 2 [ITGB2], family with sequence similarity 133 member A [FAM133A], and tumor protein p53 [TP53]), was finally constructed to forecast clinical outcomes of CC. Its predictive capability was further assessed and validated using the Gene Expression Omnibus validation set. In conclusion, IGRPM may be a promising prognostic signature to predict the prognoses and responses to immunotherapy of patients with CC. Moreover, the multi-omics study showed that IGRPM could be a novel therapeutic target for CC, which is a promising biomarker for indicating the immune-dominant status of the TME and revealing the potential mechanisms responsible for the tumorigenesis and progression of CC.

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Section: Discussionmentioning

confidence: 99%

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

Shen

2021

Front. Genet.

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“…The discrepancy between our result and the previous study might result from the important but opposing roles of CCR7 in disease. The CCR7 axis could combat the spread of cancer by trafficking of effecter cells involved in mounting an immune response to a growing tumor, while contribute to the expansion of cancer via controlling the migration of tumor cells towards the lymphatic system and metastasis (Salem et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of the Prognostic Index Based on Inflammation-Related Gene Analysis in Idiopathic Pulmonary Fibrosis

Chen

Tang

et al. 2021

Front. Mol. Biosci.

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Background: Historically, idiopathic pulmonary fibrosis (IPF) was considered a chronic inflammation disorder, but this conception was reassessed in the past decades. Our understanding of the role of inflammation in IPF and its association with clinical significance remained incomplete.Methods: We downloaded mRNA expression data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus (GEO) repository. Inflammation-related genes (IRGs) expressed differently between IPF and control (CTRL) were determined. In this study, we systemically analyzed the expression of differently expressed IRGs by comprehensive bioinformatic analysis, and then investigated their potential prognostic values. The related prognostic gene expressions were verified in our cohort.Results: 110 differently expressed IRGs were identified in this study, including 64 upregulated and 46 downregulated IRGs. Three IRGs (S100A12, CCR7, and TNFSF4) were identified as potential hub genes for prognosis. Those genes were subsequently subjected to the construction of the prognostic models. In the results, IPF patients categorized as high risk demonstrated a poor overall survival rate compared to patients categorized as low risk. Based on this prognostic model, the area under the curve (AUC) of the survival-dependent receiver operator characteristic (ROC) for 1-year, 2-year, and 3-year survival rates was 0.611, 0.695, and 0.681, respectively, in the GSE28042 cohort. These observations were validated in the GSE27957 cohort, confirming the good prognostic effect of this model. The expression of the three genes was validated in our cohort. We also conducted a nomogram based on the three IRGs’ mRNA for quantitative IPF prognosis.Conclusion: Three IRGs (S100A12, CCR7, and TNFSF4) were identified as potential markers for the prognosis of IPF.

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“…Ectopic expression of CCR7 is implicated in tumour growth and metastasis. As reviewed by A. Salem et al [ 40 ], there is a correlation of high expression of CCR7 and lymph node metastasis in various cancers such as breast, pancreatic and lung cancers. CCL19 and CCL21 are well-known cognate ligands of CCR7.…”

Section: Ccl19 and Ccl21/ccr7mentioning

confidence: 99%

Latest update on chemokine receptors as therapeutic targets

Lai

Müeller

2021

Biochemical Society Transactions

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The chemokine system plays a fundamental role in a diverse range of physiological processes, such as homeostasis and immune responses. Dysregulation in the chemokine system has been linked to inflammatory diseases and cancer, which renders chemokine receptors to be considered as therapeutic targets. In the past two decades, around 45 drugs targeting chemokine receptors have been developed, yet only three are clinically approved. The challenging factors include the limited understanding of aberrant chemokine signalling in malignant diseases, high redundancy of the chemokine system, differences between cell types and non-specific binding of the chemokine receptor antagonists due to the broad ligand-binding pockets. In recent years, emerging studies attempt to characterise the chemokine ligand–receptor interactions and the downstream signalling protein–protein interactions, aiming to fine tuning to the promiscuous interplay of the chemokine system for the development of precision medicine. This review will outline the updates on the mechanistic insights in the chemokine system and propose some potential strategies in the future development of targeted therapy.

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CCR7 as a therapeutic target in Cancer

Cited by 67 publications

References 270 publications

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment

Development and Validation of the Prognostic Index Based on Inflammation-Related Gene Analysis in Idiopathic Pulmonary Fibrosis

Latest update on chemokine receptors as therapeutic targets

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