TY - JOUR

T1 - Immune effects of α and β radionuclides in metastatic prostate cancer

AU - Lunj, Sapna

AU - Smith, Tim

AU - Reeves, Kimberley

AU - Currell, Fred

AU - Honeychurch, jamie

AU - Hoskin, Peter

AU - Choudhury, Ananya

PY - 2024/8/27

Y1 - 2024/8/27

N2 - External beam radiotherapy is used for radical treatment of organconfned prostate cancer and to treat lesions in metastatic diseasewhereas molecular radiotherapy with labelled prostate-specifcmembrane antigen ligands and radium-223 (223Ra) is indicatedfor metastatic prostate cancer and has demonstrated substantialimprovements in symptom control and overall survival comparedwith standard-of-care treatment. Prostate cancer is consideredan immunologically cold tumour, so limited studies investigatingthe treatment-induced efects on the immune response have beencompleted. However, emerging data support the idea that radiotherapyinduces an immune response in prostate cancer, but whether theresponse is an antitumour or pro-tumour response is dependent onthe radiotherapy regime and is also cell-line dependent. In vitro datademonstrate that single-dose radiotherapy regimes induce a greaterimmune-suppressive profle than fractionated regimes; less is knownabout the immune response induced by molecular radiotherapyagents, but evidence suggests that these agents might induce animmune-suppressive systemic immune response, indicated byincreased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could beassociated with clinical response. Diferent radiotherapy modalities caninduce distinct immune profles, which can either activate or suppressimmune-mediated tumour killing and the current preclinical modelsused for prostate cancer research are not yet optimal for studying thecomplexity of the radiotherapy-induced immune response.

AB - External beam radiotherapy is used for radical treatment of organconfned prostate cancer and to treat lesions in metastatic diseasewhereas molecular radiotherapy with labelled prostate-specifcmembrane antigen ligands and radium-223 (223Ra) is indicatedfor metastatic prostate cancer and has demonstrated substantialimprovements in symptom control and overall survival comparedwith standard-of-care treatment. Prostate cancer is consideredan immunologically cold tumour, so limited studies investigatingthe treatment-induced efects on the immune response have beencompleted. However, emerging data support the idea that radiotherapyinduces an immune response in prostate cancer, but whether theresponse is an antitumour or pro-tumour response is dependent onthe radiotherapy regime and is also cell-line dependent. In vitro datademonstrate that single-dose radiotherapy regimes induce a greaterimmune-suppressive profle than fractionated regimes; less is knownabout the immune response induced by molecular radiotherapyagents, but evidence suggests that these agents might induce animmune-suppressive systemic immune response, indicated byincreased expression of inhibitory checkpoint molecules such as programmed cell death 1 ligand 1 and 2, and that these changes could beassociated with clinical response. Diferent radiotherapy modalities caninduce distinct immune profles, which can either activate or suppressimmune-mediated tumour killing and the current preclinical modelsused for prostate cancer research are not yet optimal for studying thecomplexity of the radiotherapy-induced immune response.

U2 - 10.1038/s41585-024-00924-5

DO - 10.1038/s41585-024-00924-5

M3 - Review article

JO - Nature Reviews Urology

JF - Nature Reviews Urology

SN - 1759-4820

ER -