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

Abstract

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.

Inter‐ and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma

“…Programmed death ligand 1 (PD‐L1) is a transmembrane protein expressed on immune cells (IC) and tumour cells (TC), whereas programmed cell death (PD)‐1 is expressed on IC and its expression can be induced following T cell activation. Upon binding to the receptor PD‐1 in IC, the overexpressed PD‐L1 in TC leads to functional inactivation of T cells and down‐regulation of T cell antitumoral activity, resulting in immune evasion . In recent years, PD‐L1 and PD‐1 have emerged as a key check‐point that can be manipulated with inhibitory monoclonal antibodies in various cancer types.…”

Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy

“…However, there are several reports that paclitaxel-based chemotherapy has had some effectiveness in terms of improvement of quality of life and prognosis in patients with cisplatin-resistant UC (18,23). In recent years, immune-checkpoint inhibitors have been reported as a novel treatment modality for patients with advanced UC, including platinum-treated advanced UC (21,22). Many investigators and urologists have a great hope of increasing survival with these new agents in patients with advanced and cisplatinresistant UC; however, more careful evaluation of costeffectiveness, useful biomarkers, and safety are essential for standardization (21).…”

“…Although no second-line regimen for cisplatin-resistant UC hast yet been established, several clinical studies have demonstrated that paclitaxel-based chemotherapy is useful for improving the quality of life and prognosis in patients with cisplatin-resistant UC (18)(19)(20). In recent years, the efficacy of immune-checkpoint inhibitors was reported in patients with advanced UC (21,22). There is general agreement that this new tool is an epoch-changing therapeutic strategy for these patients.…”

PD‐1 blockade enhances the antitumor efficacy of GM‐CSF surface‐modified bladder cancer stem cells vaccine

“…Some studies have reported the therapeutic efficacy of anti‐PD‐1 monotherapy against BCa in mouse models . However, PD‐1 blockade alone has no significant antitumor effect, likely because PD‐1 pathway blockade does not induce a sufficiently strong antitumor response to delay BCa growth . In addition, anti‐PD‐1 monotherapy increased the percentage of CD4 + Foxp3 + T‐cells.…”