IL-1-driven systemic inflammation in tumour progression and metastatic spread

Inflammation is a fundamental immune response that protects against injury and infection; however, when unresolved, it can contribute to disease pathogenesis. Chronic inflammation is a hallmark of cancer that promotes tumour initiation and metastatic spread. Notably, this relationship is bidirectional: while chronic inflammation can promote tumour initiation, tumours themselves actively drive systemic inflammation. Two related members of the interleukin-1 (IL-1) family, IL-1α and IL-1β, are pleiotropic cytokines that link local tumour activity to systemic immune dysregulation and have emerged as principal drivers of this process. Tumour-derived IL-1β reshapes haematopoiesis in the bone marrow, promoting myeloid-skewed output and the expansion and polarisation of monocytes and neutrophils. These tumour-educated myeloid cells actively contribute to disease progression and metastatic spread through a range of mechanisms including suppression of anti-tumour immunity. In this review, we synthesise the current understanding of how tumours induce IL-1 production and how IL-1-driven systemic inflammation remodels the tumour macro-environment. We highlight emerging evidence that myeloid cell reprogramming occurs in a layered process, proposing a model of hierarchical myeloid education across the bone marrow and peripheral tissues and outline the therapeutic potential of targeting IL-1 signalling to disrupt tumour-promoting inflammation.