Roles of CCR10/CCL27–CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives

Abstract

Cancer is now one of the major causes of death across the globe. The imbalance of cytokine and chemokine secretion has been reported to be involved in cancer development. Meanwhile, CC chemokines have received considerable interest in cancer research. CCR10, as the latest identified CC chemokine receptor (CCR), has been implicated in the recruitment and infiltration of immune cells, especially lymphocytes, into epithelia such as skin via ligation to two ligands, CCL27 and CCL28. Other than homoeostatic function, several mechanisms have been shown to dysregulate CCR10/CCL27–CCL28 expression in the tumour microenvironment. As such, these receptors and ligands mediate T-cell trafficking in the tumour microenvironment. Depending on the types of lymphocytes recruited, CCR10/CCL27–CCL28 interaction has been shown to play conflicting roles in cancer development. If they were T helper and cytotoxic T cells and natural killer cells, the role of this axis would be tumour-suppressive. In contrast, if CCR10/CCL27–CCL28 recruited regulatory T cells, cancer-associated fibroblasts or myeloid-derived suppressor cells, it would lead to tumour progression. In addition to the trafficking of lymphocytes and immune cells, CCR10 also leads to the migration of tumour cells or endothelial cells (called angiogenesis and lymphangiogenesis) to promote tumour metastasis. Furthermore, CCR10 signalling triggers tumour-promoting signalling such as PI3K/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase, resulting in tumour cell growth. Since CCR10/CCL27–CCL28 is dysregulated in the tumour tissues, it is suggested that analysis and measurement of them might predict tumour development. Finally, it is hoped using therapeutic approaches based on this axis might increase our knowledge to overcome tumour progression.

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

“… 29 CCR10/CTACK interaction may relate to the development of sarcopenia due to their crucial roles in regulating multiple immune cells with conflicting effects, including helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid‐derived suppressor cells and so on. 30 However, few studies have reported the relationships between CTACK and sarcopenia. More research is needed to elucidate the relationships.…”

“…CTACK–CCR10 signalling is involved in the regulation of immune responses, including the recruitment of T cells to the skin during inflammation and the formation of immunological synapses between dendritic cells and T cells 29 . CCR10/CTACK interaction may relate to the development of sarcopenia due to their crucial roles in regulating multiple immune cells with conflicting effects, including helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid‐derived suppressor cells and so on 30 . However, few studies have reported the relationships between CTACK and sarcopenia.…”