A primer on tumour immunology and prostate cancer immunotherapy

Prostate cancer is the most commonly diagnosed non-cutaneous malignancy and the third leading cause of cancer death in Canadian men.1 Despite this incidence and the significant health burden associated with prostate cancer, its management over the last decade has become increasingly complex and controversial for both early and advanced disease. Recent recommendations questioning the benefit of prostate-specific antigen (PSA) screening2 have highlighted the requirement to uncouple the diagnosis from treatment for localized disease in order to reduce over-treatment of biologically indolent disease.3 In the meanwhile, trends to decreased screening in an aging population could result in significant increases in men with more advanced disease requiring salvage or palliative treatment, including androgen-deprivation therapy (ADT) and systemic chemotherapy. Despite recent interest in the earlier delivery of cytotoxic chemotherapeutics for men with advanced disease, prostate cancer remains, for the most part, androgen-dependent. In a non-curative setting, ADT remains a mainstay of treatment. Although most patients are initially responsive, progression to castration-resistant prostate cancer (CRPC) eventually occurs and is associated with a median time until death of less than three years.4 Nevertheless, this past decade has seen substantial improvements in the management of CRPC.5 Docetaxel, approved by Health Canada in 2005, was the first drug to demonstrate survival benefit for men with metastatic CRPC. An increasing understanding of the mechanisms of survival in prostate cancer cells with castrate levels of serum testosterone has led to multiple new therapies, including bone-targeted agents and next-generation androgen receptor inhibitors.5 Overall, these new therapeutic modalities have led to improvements in the quantity and quality of life of men with CRPC. Unfortunately, progression to a chemo-resistant, androgenindependent state is the norm. Exploring other therapeutics, including those processes and pathways involved in resistance to standard therapies, is key to further improving the quality and quantity of life of these patients. Immunotherapy represents one potentially innovative and complementary management strategy for those with advanced prostate cancers. In April 2010, the FDA approved Sipuleucel-T vaccine for the treatment of metastatic CRPC patients, making it the first therapeutic vaccine for any cancer.6 Less than a year later, the immune-stimulating drug ipilimumab was approved for the treatment of metastatic melanoma, ushering in even more focus on the potential of cancer immunotherapy.7 Recent advances in our understanding of immune interactions with cancer cells, leading to these and other successful therapeutic strategies to harness the power of the patient’s own immune system, mark the beginning of an exciting new era in cancer management. For urologists, medical oncologists, and other clinicians that regularly care for men with prostate cancer, remaining up-to-date with these new therapies and their underlying immunological concepts will allow them to offer, and better explain, the most appropriate therapies for their patients. Here we review the basic concepts in tumour immunology that underlie cancer immunotherapy with a primary focus on prostate cancer immunotherapies.