Effects of Mycobacterium bovis Calmette et Guérin (BCG) in oncotherapy: Bladder cancer and beyond

Abstract

The Mycobacterium bovis Bacillus Calmette et Guérin (BCG) vaccine was generated in 1921 with the efforts of a team of investigators, Albert Calmette and Camille Guérin, dedicated to the determination to develop a vaccine against active tuberculosis (TB) disease. Since then, BCG vaccination is used globally for protection against childhood and disseminated TB; however, its efficacy at protecting against pulmonary TB in adult and aging populations is highly variable. Due to the BCG generated immunity, this vaccine later proved to have an antitumor activity; though the standing mechanisms behind are still unclear. Recent studies indicate that both innate and adaptive cell responses may play an important role in BCG eradication and prevention of bladder cancer. Thus, cells such as natural killer (NK) cells, macrophages, dendritic cells, neutrophils but also MHC-restricted CD4 and CD8 T cells and γδ T cells may play an important role and can be one the main effectors in BCG therapy. Here, we discuss the role of BCG therapy in bladder cancer and other cancers, including current strategies and their impact on the generation and sustainability of protective antitumor immunity against bladder cancer.

Keywords: BCG; Bladder cancer; Mycobacterium bovis; Treatment.

Fig. 1.

BCG induced immune response in the tumor. BCG bacilli are internalized by urothelial cells and bladder cancer cells, generating an innate inflammatory response attracting local and peripheral NK cells, macrophages, neutrophils and proliferated/primed CD4 + T cells to the tumor site. In this scenario, BCG bacilli encounter dendritic cells (or DCs). After BCG-phagocytosis, DCs process BCG and present antigens to MHC-II restricted CD4 + T cells and at the same time initiate a Th1-type immune response through inflammatory cytokines required for effective BCG-induced antitumor activity, but simultaneously this inflammatory response could cause adverse effects to the host. At the same time, apoptotic BCG-infected tumor cells will be pyrocytosed by DCs and tumor-specific Ag/BCG-specific Ag will be presented via MHC-I to cytolytic CD8 + T cells. Tumor-Ags can also be directly detected or detected in the context of MHC by T cells, generating anti-tumor cytotoxic responses. DC, Dendritic cells; GAG layer, glycosaminoglycan; MU, Macrophages; N, Neutrophils; NK, Natural Killer cells. Note: Drawing not at scale.