Innate and adaptive immune system components activated by intravesical BCG

The innate and adaptive immune system components activated by intravesical BCG represent a complex multicellular cascade used primarily for the treatment of non-muscle invasive bladder cancer (NMIBC) (Redelman-Sidi et al., 2014). Upon administration, the live attenuated Mycobacterium bovis (BCG) binds to the bladder lining via fibronectin and is internalized by both normal and malignant urothelial cells, as well as resident macrophages (Pettenati & Ingersoll, 2018). This interaction initiates an innate response characterized by the recruitment of neutrophils and natural killer (NK) cells, followed by a robust adaptive immune response dominated by Th1-type cytokines such as interferon-gamma and interleukin-12 (Fuge et al., 2015). These components work in concert to induce tumor cell apoptosis and create a long-term immunosurveillance environment that prevents cancer recurrence (Kamat et al., 2015). While highly effective, the activation of these systems can lead to significant side effects, ranging from local irritation to life-threatening systemic BCG infection known as BCGosis (Larsen et al., 2020).

Other names

BCG-induced immune responseIntravesical BCG immunotherapy mechanismBCG-mediated antitumor immunityBacillus Calmette-Guérin-induced immunity

The mechanism involves the attachment of BCG to the bladder wall via fibronectin, followed by internalization into urothelial and tumor cells. This triggers a robust innate immune response (neutrophils, macrophages, NK cells) and a subsequent adaptive Th1-polarized response (CD4+ and CD8+ T cells), leading to the secretion of pro-inflammatory cytokines and direct tumor cell lysis.