Immunotherapy in prostate cancer: new horizon of hurdles and hopes

Abstract

Purpose: Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field.

Methods: We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses.

Results: Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet.

Conclusion: Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.

Keywords: Immune checkpoints; Immunotherapy; PD-1; PD-L1; Prostate cancer; Vaccine.