Interleukin-1 beta signaling in cancer: A double-edged sword in inflammation and tumorigenesis

Interleukin-1 beta (IL-1β) is a central pro-inflammatory cytokine with critical roles in immune regulation, inflammation, and tumor biology. Synthesized as an inactive precursor and activated through inflammasome-mediated cleavage, IL-1β signals via the IL-1 receptor to orchestrate immune responses. While essential for host defense, sustained IL-1β activity in the tumor microenvironment promotes angiogenesis, metastasis, epithelial–mesenchymal transition, and immune suppression, thereby facilitating the progression of cancers such as breast, lung, pancreatic, and colorectal. Conversely, IL-1β can enhance anti-tumor immunity by driving dendritic cell maturation, T-cell priming, and pyroptosis, thereby contributing to beneficial immune surveillance in certain hematologic malignancies. This dual role presents both challenges and opportunities for therapeutic intervention. Clinical blockade of IL-1β with agents such as anakinra, canakinumab, and rilonacept has shown promise, notably in the CANTOS trial, where IL-1β inhibition was associated with a reduction in lung cancer incidence. However, outcomes in colorectal and pancreatic cancer remain variable. The potential for immune suppression, combined with the absence of predictive biomarkers, underscores the need for precision-based strategies. Emerging approaches, including serum and tissue IL-1β profiling, analysis of inflammasome components, liquid biopsy, spatial transcriptomics, and single-cell technologies, may enable context-specific modulation. This review synthesizes current understanding of IL-1β’s paradoxical functions in cancer, evaluates therapeutic strategies targeting its signaling axis, and highlights future directions for integrating IL-1β modulation into precision oncology.