CXC Chemokine Receptors in the Tumor Microenvironment and an Update of Antagonist Development

Xiao, Yang; Yang, Hua; Li, Jiekai; Wu, Fengjie; Liu, Fang

doi:10.1007/112_2020_35

Cited by 21 publications

(19 citation statements)

References 192 publications

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“…Via complex mechanisms, these communications were involved in tumor growth, immune escape, and therapeutic efficacy ( 83 ). Intercellular communication between CXC chemokines and TME affects the patterns of proliferation and apoptosis in various tumor cell types, thus facilitating specific biological mechanism for tumor invasion and metastasis ( 14 ). In the TME, CXC chemokines regulate tumor angiogenesis, modulate inflammation and immunity, and participate in the formation of non-vascular tumor stroma.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, modifying the factors and cells in the TME during the management of malignancies can improve the effectiveness of drug treatment ( 13 ). As an essential subunit of the chemokine family, the CXC chemokines can modulate the TME and biological phenotypes, affecting tumorigenesis, tumor-related therapeutic effect, tumor metastasis, and patient outcomes ( 14 ). Moreover, within the TME, CXC chemokine expression is often altered compared to normal tissue.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma

et al. 2021

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BackgroundPancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified.MethodsBioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer.ResultsExcept for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times.ConclusionsThese findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma

et al. 2021

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“…CXCR6-CXCL16 axis also recruits immune cells to cancer sites just like the way of other CXCRs, thereby affecting the progression of cancer. However, the cell-speci c functions of CXCR6 remain unclear to a large extent (40).…”

Section: Discussionmentioning

confidence: 99%

Expression Profile and Prognostic Value of CXCR Family Members in Head and Neck Squamous Cell Carcinoma

Shen

Zhou

Cao

et al. 2021

Preprint

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Background: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). Methods: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). Results: CXCRs were differentially expressed in HNSCC. As shown by Kaplan Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. Conclusions: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

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Section: Introductionmentioning

confidence: 99%

“…Hodgkin and Reed-Sternberg (H/RS) cells, although only accounting for less than 1% of total HL tumor cells, contribute considerably to tumor progression [1]. The mechanism may involve immune escaping which was conducted by interaction of various cytokines and chemokines between tumor cells and inflammatory cells in the tumor microenvironment [2].Accumulating evidence suggests that chemokine ligands interact with corresponding receptors to induce a variety of cell responses that affect tumor progression, such as cell proliferation, migration, invasion and metastasis. CXCL16 is a chemokine that exists in two forms: a transmembrane form (TM-CXCL16) and a soluble form (sCXCL16) which is secreted into the cell culture supernatant via the cleavage of TM-CXCL16 by a disintegrin-like metalloproteinase 10 (ADAM10) [3].…”

mentioning

confidence: 99%

CXC Chemokine Ligand 16 Promotes the Proliferation and Migration of Hodgkin and Reed-Sternberg Cells Via the PI3K/Akt/NF-κB Signaling Pathway

2021

NACS

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CXC Chemokine Receptors in the Tumor Microenvironment and an Update of Antagonist Development

Cited by 21 publications

References 192 publications

Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma

Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma

Expression Profile and Prognostic Value of CXCR Family Members in Head and Neck Squamous Cell Carcinoma

CXC Chemokine Ligand 16 Promotes the Proliferation and Migration of Hodgkin and Reed-Sternberg Cells Via the PI3K/Akt/NF-κB Signaling Pathway

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