BCG치료에서 방광의 면역 반응에 대한 이해

Abstract

Though BCG (bacille de Calmette-Guerin) therapy has been the standard of care for high-risk non-muscle invasive bladder cancer for more than 35 years, its precise mechanisms of action remain unclear. It is however well established that it involves an immune response from the tumor-bearing host and I review the current knowledge based on human observational trials and experimental studies in mice. Recent studies reported that the vast majority of BCG was voided after instillation, and, among the few bacteria that persist, their internalization by urothelial cells remained questionable and understudied. Knowledge about the mechanism of BCG internalization is scarce and controversial and there is no data about the fate of BCG following internalization by urothelial cells. Despite this low level of internalization, a strong immune response is triggered following repeated intravesical BCG. Through several in vitro and orthotopic mice model studies, it is suggested that BCG-mediated anti-tumor activity involves an immune response that is characterized by waves of inflammatory cells shortly after each repeated instillation, followed by the establishment of a Th1 polarized environment. Whether the effective eradication of tumor cells involves some tumor-specific killing or whether BCG therapy functions as a nonspecific immunotherapy is not yet clear.