External beam radiotherapy is used for radical treatment of organ-confined prostate cancer and to treat lesions in metastatic disease whereas molecular radiotherapy with labelled prostate-specific membrane antigen ligands and radium-223 (223Ra) is indicated for metastatic prostate cancer and has demonstrated substantial improvements in symptom control and overall survival compared with standard-of-care treatment. Prostate cancer is considered an immunologically cold tumour, so limited studies investigating the treatment-induced effects on the immune response have been completed. However, emerging data support the idea that radiotherapy induces an immune response in prostate cancer, but whether the response is an antitumour or pro-tumour response is dependent on the radiotherapy regime and is also cell-line dependent. In vitro data demonstrate that single-dose radiotherapy regimes induce a greater immune-suppressive profile than fractionated regimes; less is known about the immune response induced by molecular radiotherapy agents, but evidence suggests that these agents might induce an immune-suppressive systemic immune response, indicated by increased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could be associated with clinical response. Different radiotherapy modalities can induce distinct immune profiles, which can either activate or suppress immune-mediated tumour killing and the current preclinical models used for prostate cancer research are not yet optimal for studying the complexity of the radiotherapy-induced immune response.
Nature reviews. Urology. 2024 Aug 27 [Epub ahead of print]
Sapna Lunj, Tim Andrew Davies Smith, Kimberley Jayne Reeves, Fred Currell, Jamie Honeychurch, Peter Hoskin, Ananya Choudhury
Division of Cancer Sciences, Oglesby Cancer Research Building, University of Manchester, Manchester, UK. ., Nuclear Futures Institute, School of Computer Science and Engineering, Bangor University, Bangor, UK., Division of Cancer Sciences, Paterson Building, University of Manchester, Manchester, UK., The Dalton Cumbria Facility and the Department of Chemistry, University of Manchester, Manchester, UK., Division of Cancer Sciences, Oglesby Cancer Research Building, University of Manchester, Manchester, UK.