A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now.

The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated. Several checkpoint targets (programmed death ligand-1 [PD-L1] programmed cell death protien-1 [PD-1], and cytotoxic T-lymphocyte associated protein 4 [CTLA4]) have received the most attention in the treatment of bladder cancer, and have inhibitor agents either approved or in late-stage development. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in immune system functioning.

Bellmunt J ，Powles T ，Vogelzang NJ 《-》

Checkpoint inhibitors: the new treatment paradigm for urothelial bladder cancer.

Katz H ，Wassie E ，Alsharedi M 《-》

Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway.

Barclay J ，Creswell J ，León J 《ARCHIVOS ESPANOLES DE UROLOGIA》

A review of the PD-1/PD-L1 checkpoint in bladder cancer: From mediator of immune escape to target for treatment.

Recent observations have focused attention on the means that human tumors employ to evade host defense systems critical to immune surveillance. The concepts of immunotherapy are familiar to urologists because of the use of bacillus Calmette-Guérin in bladder cancer. Research demonstrating the importance of checkpoint inhibitors in suppressing immune responses against tumors has heightened interest in immunotherapy at a time when there is a need for alternatives to bacillus Calmette-Guérin. We review the literature on the application of immunotherapeutic agents targeting a key checkpoint pathway, programmed death 1 (PD-1) and its ligand (PD-L1), in the field of bladder cancer. A comprehensive literature review was performed using Medline/Pubmed and Embase. The PD-1/PD-L1 pathway may be manipulated by cancer cells to subvert the immune system. PD-1/PD-L1 blockade has been tested in clinical trials for various malignancies including metastatic urothelial carcinoma, with significant response rates and limited side effects. PD-L1 expression has also been proposed as a prognostic marker for bladder cancer with mixed results. PD-1 is one of several key receptors mediating immune escape, and agents targeting its ligand PD-L1 have already been successfully applied to patients with metastatic urothelial cancer. More research is needed to standardize criteria for PD-L1 positivity, explore its use as a biomarker, and optimize its use in the treatment for bladder cancer.

Zhou TC ，Sankin AI ，Porcelli SA ，Perlin DS ，Schoenberg MP ，Zang X ... -  《-》

Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

Koshkin VS ，Grivas P 《-》