Prostate cancer affects one in six men. Advanced prostate cancer invariably progresses to castration resistant prostate cancer (CRPC), which is lethal due to treatment resistance. There is an unmet need in CRPC to develop new therapies that improve outcome.
Cancer immunotherapies that block immune checkpoints and release T cell effector function such as anti-CTLA-4 mAb (ipilimumab) and the anti-PD-1 mAbs (nivolumab, pembrolizumab) have been designated breakthrough treatments for many cancers because of the durable responses and unprecedented survival benefit. However, in prostate cancer, these immune checkpoint inhibitors remain relatively poorly developed and efficacy to single immune checkpoint blockade has generally been poor. This has been attributed to the low mutational load and PD-L1 expression in prostate cancer.
Although the presence of inflammatory cells have been detected in prostate cancer tissues implying that this tumour is subject to a host immune response, the relative proportion and quality of prostate infiltrating immune cells in mCRPC has not been well characterised. Furthermore, the tumour microenvironment of prostate cancer may be more immunosuppressive than other tumour types and thus the immune response may be undermined by other factors. To enhance responses in a greater proportion of patients with metastatic CRPC, it is critical to define the immune infiltrates and microenvironment within prostate cancer, to allow novel combinations of immunotherapeutic strategies to be rationally designed. I will outline the recent and ongoing efforts to develop immune therapies for patients with prostate cancer.