Multifaceted Roles of Chemokine C-X-C Motif Ligand 7 in Inflammatory Diseases and Cancer

Abstract

Over recent years, C-X-C motif ligand 7 (CXCL7) has received widespread attention as a chemokine involved in inflammatory responses. Abnormal production of the chemokine CXCL7 has been identified in different inflammatory diseases; nevertheless, the exact role of CXCL7 in the pathogenesis of inflammatory diseases is not fully understood. Persistent infection or chronic inflammation can induce tumorigenesis and progression. Previous studies have shown that the pro-inflammatory chemokine CXCL7 is also expressed by malignant tumor cells and that binding of CXCL7 to its cognate receptors C-X-C chemokine receptor 1 (CXCR1) and C-X-C chemokine receptor 2 (CXCR2) can influence tumor biological behavior (proliferation, invasion, metastasis, and tumor angiogenesis) in an autocrine and paracrine manner. CXCL7 and its receptor CXCR1/CXCR2, which are aberrantly expressed in tumors, may represent new targets for clinical tumor immunotherapy.

Peripheral monocyte transcriptomics associated with immune checkpoint blockade outcomes in metastatic melanoma

“…We did not identify a distinct intermediate monocyte population on high-level unsupervised clustering, however unsupervised clustering of the large classical monocyte compartment revealed further heterogeneity within it. We found the classical monocyte compartment could be further divided into four distinct sub-clusters: ‘Classical1’ characterised by high expression of alarmin complex genes S100A8/A9 ; ‘Classical2’ with high expression of CD14 and EGR1, a key inhibitory regulator of myeloid populations 28 ; ‘Classical3’ with robust expression of an IFN-response associated signature including GBP1, GBP2, and STAT1 ; and ‘Classical4’ which had a distinct monocyte-platelet aggregate (MPA)-like classical profile with high expression of platelet-associated genes including PPBP (P adj = 9.5×10 -159 ) which encodes chemokine and CXCR1/CXCR2 ligand CXCL7 in activated platelets 26 , and GP9 (P adj = 2.3×10 -38 ), a von Willebrand factor receptor required for clotting 27 (Figure 5A & 5B, Supplementary Table 19). Pathway enrichment analysis of group-defining markers demonstrated overlap between groups, but Classical1 was characterised by enrichment of antimicrobial humoral response pathway, Classical2 for phagocytosis, Classical3 for defense response to virus, antigen processing via MHC class II and T cell co-stimulation (Figure 5C, Supplementary Table 21) whilst Classical4 was enriched for platelet activation and blood coagulation pathways (Figure 5C, Supplementary Table 21).…”

“…We did not identify a distinct intermediate monocyte population on high-level unsupervised clustering, however unsupervised clustering of the large classical monocyte compartment revealed further heterogeneity within it. We found the classical monocyte compartment could be further divided into four distinct sub-clusters: 'Classical1' characterised by high expression of alarmin complex genes S100A8/A9 ; 'Classical2' with high expression of CD14 and EGR1, a key inhibitory regulator of myeloid populations 28 ; 'Classical3' with robust expression of an IFN-response associated signature including GBP1, GBP2, and STAT1; and 'Classical4' which had a distinct monocyte-platelet aggregate (MPA)-like classical profile with high expression of plateletassociated genes including PPBP (Padj = 9.5x10 -159 ) which encodes chemokine and CXCR1/CXCR2 ligand CXCL7 in activated platelets 26 , and GP9 (Padj = 2.3x10 -38 ), a von Willebrand factor receptor required for clotting 27 (Figure 5A & 5B, Supplementary Table 19).…”

Immune‐Hot tumor features associated with recurrence in early‐stage ovarian clear cell carcinoma

“…CXCL2 (GROb) and CXCL3 (GROg) are variants of a growth‐regulated oncogene (GRO) 14 . CXCL2, CXCL3 and CXCL7 all show strong binding affinity to CXCR2 as their cognate receptor to transduce downstream signals 14,15 . All three chemokines have been known to recruit neutrophils to the tumor microenvironment (TME).…”

“…14 CXCL2, CXCL3 and CXCL7 all show strong binding affinity to CXCR2 as their cognate receptor to transduce downstream signals. 14,15 All three chemokines have been known to recruit neutrophils to the tumor microenvironment (TME). OSM, the gene coding for a secreted cytokine oncostatin-M known to promote tumor progression by reprogramming the TME was also significantly upregulated in early-stage OCCC with recurrence.…”

Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer

“…CCR7 is a G protein-coupled receptor with seven transmembrane domains. Its physiological effects are mediated by binding to its two ligands, CCL19 and CCL8, at the extracellular N terminus[ 42 ]. CCR7 is expressed in both tumour and lymphoid tissues and activates B and T lymphocyte migration towards CCR7 ligands (CCL19 and CCL21) [ 42 ].…”