The Role of Interleukin-1 in the Pathogenesis of Cancer and its Potential as a Therapeutic Target in Clinical Practice

Abstract

Interleukin-1 (IL-1) has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors. Overexpression of the IL-1 agonists IL-1a and IL-1b has been shown to promote tumor invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors. IL-1 blockers such as anakinra and canakinumab are already approved and widely used for the treatment of some autoimmune and autoinflammatory diseases and are currently being tested in preclinical and human clinical trials for cancer therapy. In this paper we review the most recent discoveries regarding the association between IL-1 dysregulation and cancer and present the novel IL-1 blockers currently being tested in cancer therapy and their corresponding clinical trials.

Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

“…In order to investigate potential role of soluble molecules on thrombocytosis development, we have further analyzed systemic concentrations of cytokines of interest. IL-1 is potent cytokine involved in variety of pro-inflammatory processes, but also in tumorigenesis and tumor progression 25 . Besides direct stimulating effect on tumor cell proliferation, it has also been shown that colon cancer cell-derived IL-1α may upregulate angiogenesis by modulating stromal cells within the tumor microenvironment 15 .…”

Association of angiogenesis and inflammation‑related gene functional polymorphisms with early‑stage breast cancer prognosis

“…It was also found that high tumour co-expression of the VEGF and IL-6 family cytokines significantly lowers the human epidermal growth factor receptor 2 (HER2) negative BC survival (11). Moreover, higher expression of pro-inflammatory IL-1β cytokine is correlated with higher BC stage and significantly worse survival (12). In addition, IL-1α acts as a pro-inflammatory molecule itself and also promotes the activity of IL-1β, resulting in an increased growth of BC cells and tumour progression (13).…”

“…As far as IL-1α SNP is concerned, Um et al (18) demonstrated that the IL-1α rs1800587 CC genotype is associated with higher transcriptional activity of the IL-1α gene. Overexpression of the IL-1α promotes tumour invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors (12). A large meta-analysis performed by Xia et al (30) showed that the IL-1α rs1800587 C allele and CC genotype are associated with increased cancer risk in general.…”

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

“…The presence of OCs leads to increased local and systemic inflammation ( Figure 2 ). Within the tumor microenvironment (TME), OC cells, infiltrating immune cells and other cells including fibroblasts, endothelial cells and adipocytes continuously secrete pro‐inflammatory cytokines, including IL‐6, TNF, IL‐1, and IL‐8 58–60 . The level of these cytokines in the serum of OC patients is associated with poorer prognosis 58–60 .…”

“…Within the tumor microenvironment (TME), OC cells, infiltrating immune cells and other cells including fibroblasts, endothelial cells and adipocytes continuously secrete pro‐inflammatory cytokines, including IL‐6, TNF, IL‐1, and IL‐8 58–60 . The level of these cytokines in the serum of OC patients is associated with poorer prognosis 58–60 . High levels of IL‐6 or TNF in ascites is associated with shorter progression‐free survival 58,60 and circulating CRP levels are associated with increased risk of ovarian cancer 61,62 …”