title: Immunotherapy for urothelial cancer: from BCG to checkpoint inhibitors and beyond.
abstract: Since its introduction almost 40 years ago, intravesical BCG for non-muscle invasive bladder cancer remains one of the most successful cancer immunotherapies. However, up to 40% of patients will progress after BCG therapy and develop invasive bladder cancer. Despite its extensive clinical use, we are only beginning to understand how BCG works. Here we review preclinical and clinical data that implicate BCG-induced Th1 and cytotoxic cellular immune responses in cancer regression. We propose that future immunotherapies should aim to augment Th1 and/or cellular responses in those that fail BCG therapy. We review clinical trials of immunotherapy in bladder cancer with a focus on the promising role of checkpoint blockade inhibitors that target the programmed cell death 1/programmed death-ligand 1 (PD-L1) axis and/or cytotoxic T lymphocyte antigen 4.
authors.affiliation: Peter Gorer Department of Immunobiology, Programme of Infection and Immunity, 2nd Floor, Borough Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Deborah
authors.initials: D
authors.lastname: Enting
authors.forename: Sarah
authors.initials: S
authors.lastname: Rudman
authors.forename: Simon
authors.initials: S
authors.lastname: Chowdhury
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: CTLA-4; PD-1; PD-L1; Th1; immune checkpoint; immunoediting; immunosurveillance