Immunotherapy in prostate cancer: new horizon of hurdles and hopes
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TOPIC PAPER
Immunotherapy in prostate cancer: new horizon of hurdles and hopes Igor Tsaur1 · Maximilian P. Brandt1 · Eva Juengel1 · Cécile Manceau2 · Guillaume Ploussard2,3 Received: 14 July 2020 / Accepted: 13 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancerrelated 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 Prostate cancer · Immunotherapy · Immune checkpoints · Vaccine · PD-1 · PD-L1
Introduction Igor Tsaur and Maximilian P. Brandt have contributed equally and they are considered as first authors. * Igor Tsaur igor.tsaur@unimedizin‑mainz.de Maximilian P. Brandt maximilian.brandt@unimedizin‑mainz.de Eva Juengel eva.juengel@unimedizin‑mainz.de Cécile Manceau [email protected] Guillaume Ploussard [email protected] 1
Department of Urology and Pediatric Urology, University Medical Center, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany
2
Department of Urology, CHU-Institut Universitaire du Cancer Toulouse—Oncopole, Toulouse, France
3
Department of Urology, La Croix du Sud Hospital, Toulouse, France
Despite promising results of immunotherapy (IT) in genitourinary malignancies such as urothelial and kidney cancer, IT has not turned out to be a meaningful player in the treatment armamentarium of advanced prostate cancer (PCa) yet. The only registered agent in the field, sipuleucel-T, an immunostimulant based on dendritic cells, has shown a benefit in overall survival (OS) of almost 4 months compared to placebo in metastasiz
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