Table 1.

Summary of key steps and mediators in the mechanism of action of BCG immunotherapy

Steps in BCG activity	Mediated by
1. Infection of urothelial and/or bladder cancer cells	Fibronectin
2. Induction of immune reaction	Cell types: granulocytes, T-helper cells, dendritic cells, and macrophages Immune molecules: MHC class I, CD4+, various cytokines including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN- γ.
3. Induction of antitumor effects	Th1 cells (acquired immunity) via CD4+ T-cells and CD8+ cytotoxic T lymphocytes (driven by IL-2, TNF, IL-12, and IFN-γ)
	Th2-cell (innate immunity) through NK cells (driven by IL-4, IL-5, IL-6, and IL-10) Neutrophil recruitment (via IL-17 release) and macrophages.

Abbreviations: IL, interleukin; MHC, major histocompatibility complex; BCG, Bacillus Calmette–Guerin; NK, natural killer; TNF-α, tumor necrosis factor alpha; IFN-γ, interferon gamma.