Innate and adaptive immune pathways modulated by intravesical BCG

Intravesical Bacillus Calmette-Guérin (BCG) therapy is the gold-standard immunotherapy for high-risk non-muscle invasive bladder cancer (NMIBC). The treatment functions by initiating a complex cascade of innate and adaptive immune responses within the bladder microenvironment (Redelman-Sidi et al., 2014). Initially, BCG bacteria bind to fibronectin on the urothelial surface and are internalized by both cancer cells and macrophages, triggering innate signaling via Toll-like receptors 2 and 4 (Pettenati & Ingersoll, 2018). This activation results in the secretion of pro-inflammatory Th1 cytokines, such as interleukin-12 and interferon-gamma, which are critical for the recruitment of natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (Naranjo et al., 2022). These effector cells subsequently target and destroy residual malignant cells through direct cytotoxicity and apoptosis induction. Furthermore, recent research highlights the role of 'trained immunity,' where BCG induces long-term epigenetic reprogramming of innate immune cells to enhance anti-tumor surveillance (Netea et al., 2020). While highly effective, the therapy carries risks of local complications like chemical cystitis and rare but severe systemic infections known as BCGosis (Fuge et al., 2015).

Other names

BCG-induced immune responseBCG immunotherapy mechanismIntravesical BCG pathwaysTrained immunity in bladder cancer

Induction of a local Th1-polarized inflammatory response and trained immunity via TLR2/4 activation and cytokine release.