Biofilm-driven chronic inflammation and tumorigenesis

Biofilms of pathogenic bacteria are traditionally defined as microcolonies encased in an endogenously produced matrix upon host tissue. However, realistically, it is a highly heterogenous microenvironment composed of the bacterial cells and their extracellular polymeric substances (EPS), and host necrotic tissue, fibrotic tissue, fibrosis-associated cells and their extracellular matrix. This diverse milieu makes biofilms a potent immune evasion strategy. Its immune non-clearance can lead to relapse, potentially resulting in a persistent dysfunctional immune response; chronic inflammation. Characterised by repeated proinflammatory signalling, chronic inflammation may lead to localised or systemic instability by elevating mutagenesis and promoting anti-apoptotic pathways in host cells. This combined with the biofilm microenvironment's relative isolation from the host immune system significantly promotes tumourigenesis. The tumour microenvironment develops in continuum with the biofilm microenvironment as an immunosuppressive vascularised tissue. This tripartite pathophysiology of biofilm-induced chronic inflammation and tumourigenesis presents these clinical conditions, traditionally studied independently of each other, as an intricate web of interdependent disorder. Such interventions may include biofilm-disrupting agents, inflammatory pathway inhibitors targeting NF-κB/STAT3 signalling, and immune checkpoint-directed therapies aimed at dismantling the tumour-protective inflammatory niche.