Current Understanding of Bladder Immune Response to BCG Therapy

, Byung Hoon Chi; , In Ho Chang

Review Article

The Korean Journal of Urological Oncology 2014;12(1):16-22.
Published online April 30, 2014.

BCG치료에서 방광의 면역 반응에 대한 이해

지병훈, 장인호

중앙대학교 의과대학 비뇨기과학교실

Current Understanding of Bladder Immune Response to BCG Therapy

Byung Hoon Chi , In Ho Chang

Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea

Correspondence: In Ho Chang

Abstract

Though BCG (bacille de Calmette-Guerin) therapy has been the standard of care for high-risk non-muscle inva-sive 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 eradi-cation of tumor cells involves some tumor-specific killing or whether BCG therapy functions as a nonspecific immunotherapy is not yet clear. (Korean J Urol Oncol 2014;12:16-22)

Key Words: Bladder cancer, BCG, Immune response