Abstract
Urothelial bladder cancer (UBC) is one of the most common lethal cancer worldwide and the 5-year survival rate has not improved significantly with current treatment protocols during the last decade. Intravesical immunotherapy with Bacillus Calmette-Guérin is currently the standard care for non-muscle invasive UBC. Recently, a subset of patients with locally advanced or metastatic UBC have responded to checkpoint blockade immunotherapy against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1) or the cytotoxic T-lymphocyte antigen 4 that releases the inhibition of T cells, the remarkable clinical efficacy on UBC has brought total five checkpoint inhibitors approved by the FDA in the last 2 years, and this is revolutionizing treatment of advanced UBC. We discuss the rationale for immunotherapy in bladder cancer, progress with blocking the PD-1/PD-L1 pathway for UBC treatment, and ongoing clinical trials. We highlight the complexity of the interactions between cancer cells and the immune system, the genomic basis for response to checkpoint blockade immunotherapy, and potential biomarkers for predicting immunotherapeutic response.
Highlights
The immune system includes both innate and adaptive immunity and it can recognize and destroy malignantly transformed cells
Tcell activation is followed by interaction between specific T-cell receptor (TCR) and antigen peptides presented by the major histocompatibility complex (MHC), the CD28B7 co-stimulation increases the binding affinity of the MHC-antigen-TCR complex (Fig. 1a)
Genomic characteristics of bladder cancer, just as those of melanoma and nonsmall cell lung cancer (NSCLC), may explain the good clinical benefit resulting from immune checkpoint blockade therapy and this has been supported in a recent phase II trial of atezolizumab as a tentative first-line therapy in cisplatin-ineligible Urothelial bladder cancer (UBC) patients with locally metastatic UBC17
Summary
Urothelial bladder cancer (UBC) is one of the most common cancer of the urinary tract worldwide. Chromosomal rearrangements (e.g., FGFR3–TACC3 fusion gene) and viral integration (e.g., HPV16) are recurrent structural variants in UBC These genomic alterations change the hallmarks of cancer fundamental cellular pathways such as the p53/RB cell cycle pathway, the RTK/PI3K/mTOR proliferative pathway, and the histone modification chromatin regulatory network, which become potential druggable targets for UBC25, but they produce many non-self, or “foreign” proteins, which could be recognized by activated effector T cells and potentiate cancer cells responding to immune checkpoint inhibitors[26]. Genomic characteristics of bladder cancer, just as those of melanoma and NSCLC, may explain the good clinical benefit resulting from immune checkpoint blockade therapy and this has been supported in a recent phase II trial of atezolizumab as a tentative first-line therapy in cisplatin-ineligible UBC patients with locally metastatic UBC17. The impressive antitumor responses to checkpoint blockades of CTLA-4, PD-1, and PD-L1 have been seen in metastatic melanoma[10], advanced NSCLC, renal cancer[11], as well as in advanced bladder cancer[12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
