External beam radiotherapy is used for radical treatment of organconfned prostate cancer and to treat lesions in metastatic disease
whereas molecular radiotherapy with labelled prostate-specifc
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 efects 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 profle 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. Diferent radiotherapy modalities can
induce distinct immune profles, 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.