Chronic inflammation supports tissue repair while inadvertently promoting carcinogenesis. Cytokines - critical immune system-signaling molecules - mediate the inflammatory response and establish a cancer-conducive microenvironment. Proinflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interleukin-1β, are frequently overexpressed in chronic inflammation and facilitate tumor progression through cell proliferation, survival, angiogenesis, and metastasis. Anti-inflammatory cytokines (e.g., interleukin-10) suppress immune surveillance, which predisposes to tumor growth. Chronic inflammation-induced dysregulation of cytokine networks induces sustained transcriptional factor activation (e.g., nuclear factor-kappa B and signal transducer and activator of transcription 3) that orchestrate gene expression for cell survival and immune evasion. Cytokines influence immune cell recruitment and polarization for immunosuppression and tumor promotion. Emerging evidence highlights the role of cytokines in epithelial-to-mesenchymal transition, a key process in metastasis. Targeting the cytokine-signaling pathway constitutes a promising cancer treatment option. Monoclonal antibodies and small-molecule cytokine inhibitors and their receptors could mitigate tumor-promoting inflammation. Understanding the complex interplay among chronic inflammation, cytokines, and cancer progression is critical for identifying biomarkers and developing targeted therapies to improve clinical outcomes. This review underscores the significance of cytokines in the chronic inflammation-cancer linkage and as potential therapeutic targets. Further research is essential to elucidate intricate cytokine mechanisms in the inflammatory tumor microenvironment for clinical interventions.
Nakase et al. (2025) studied this question.