CCL18 in the Progression of Cancer

Abstract

A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvironment and an important element of cancer immune evasion. Consequently, elevated levels of CCL18 in the serum and the tumor are connected with a worse prognosis for the patient. This paper shows the importance of CCL18 in neoplastic processes. It includes a description of the signal transduction from PITPNM3 in CCL18-dependent migration, invasion, and epithelial-to-mesenchymal transition (EMT) cancer cells. The importance of CCL18 in angiogenesis has also been described. The paper also describes the effect of CCL18 on the recruitment to the cancer niche and the functioning of cells such as TAMs, regulatory T cells (Treg), cancer-associated fibroblasts (CAFs) and tumor-associated dendritic cells (TADCs). The last part of the paper describes the possibility of using CCL18 as a therapeutic target during anti-cancer therapy.

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer

“…M2-like macrophages can produce cytokines including TGF-β and IL-10 to promote tumor growth ( 47 , 48 ). In addition, different kind of chemokines from M2-like macrophages including CCL18 and CCL22 mediate immune cells migration to tumor microenvironment ( 49 ). In the present study, we found that PD-1 high ILC2 culture supernatant enhanced the expression of MRC1 (encoding CD206, a typical marker of M2 macrophages) and other M2 macrophage related genes ( TGFB1 , CCL18 , and ARG1 ), and diminished the expression of M1 macrophage related genes ( TNF , IL6 , and CCL5 ).…”

Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis

“…Recently, Amorim et al investigated the role of NLRP3 in human PCM and found that hypoxic cells from patients, which are characterized by the intracellular expression of hypoxia-inducible transcription factor (HIF)-1α, had higher activation of this inflammasome than the control subjects did [ 37 ]. Typically, inflamed tissue has low levels of oxygen, triggering the HIF-1α that up-regulates the IL12B gene to produce more IL-12p40, and inducing Th2 cytokines profile in DCs, which, in turn, favors the secretion of CCL18 [ 58 , 59 ]. Therefore, during active pulmonary chronic PCM, moDCs could have a high expression of HIF-1α and NLRP3, with consequential up-regulation of IL-1β that favors fibrosis and could induce the Th22 response, with IL-21 and IL-23.…”

Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance

“…This produces another major angiogenic factor called pro-matrix metalloproteinase 9 (proMMP9) ( 125 ). M2 macrophages also facilitate carcinogenesis and metastasis through the production of CCL18 ( 126 ) and the nuclear factor- κB/FAK pathway ( 127 ) leading to induction, migration, invasion, and the EMT. Lastly, TNF is a product of both activated macrophages and the cells of the TME; in addition to being an anti-cancer cytokine, it has been implicated in the inflammatory process necessary for tumor growth ( 128 ).…”