Pub Date : 2024-08-27DOI: 10.1038/s41585-024-00924-5
Sapna Lunj, Tim Andrew Davies Smith, Kimberley Jayne Reeves, Fred Currell, Jamie Honeychurch, Peter Hoskin, Ananya Choudhury
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. This Review focusses on what is known about the interactions between conventional radiotherapy and the immune system. The authors discuss how this knowledge can be applied to investigate gaps regarding the immune interactions of molecular radiotherapies.
{"title":"Immune effects of α and β radionuclides in metastatic prostate cancer","authors":"Sapna Lunj, Tim Andrew Davies Smith, Kimberley Jayne Reeves, Fred Currell, Jamie Honeychurch, Peter Hoskin, Ananya Choudhury","doi":"10.1038/s41585-024-00924-5","DOIUrl":"10.1038/s41585-024-00924-5","url":null,"abstract":"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. This Review focusses on what is known about the interactions between conventional radiotherapy and the immune system. The authors discuss how this knowledge can be applied to investigate gaps regarding the immune interactions of molecular radiotherapies.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"651-661"},"PeriodicalIF":12.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1038/s41585-024-00931-6
Louise Lloyd
{"title":"AI for drug discovery","authors":"Louise Lloyd","doi":"10.1038/s41585-024-00931-6","DOIUrl":"10.1038/s41585-024-00931-6","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 9","pages":"517-517"},"PeriodicalIF":12.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1038/s41585-024-00930-7
Maria Chiara Masone
{"title":"Utility of PSA screening in transgender women receiving oestrogens","authors":"Maria Chiara Masone","doi":"10.1038/s41585-024-00930-7","DOIUrl":"10.1038/s41585-024-00930-7","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 9","pages":"518-518"},"PeriodicalIF":12.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1038/s41585-024-00913-8
Renu S. Eapen, Scott G. Williams, Sean Macdonald, Simon P. Keam, Nathan Lawrentschuk, Lewis Au, Michael S. Hofman, Declan G. Murphy, Paul J. Neeson
High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer. Lutetium PSMA is approved for the treatment of advanced prostate cancer and is being studied in a neoadjuvant setting. The influence of lutetium PSMA on the tumour immune microenvironment is unknown. In selected patients, lutetium PSMA could be used as a stand-alone treatment or in combination with immunotherapy to produce long-lasting antitumour immunity.
{"title":"Neoadjuvant lutetium PSMA, the TIME and immune response in high-risk localized prostate cancer","authors":"Renu S. Eapen, Scott G. Williams, Sean Macdonald, Simon P. Keam, Nathan Lawrentschuk, Lewis Au, Michael S. Hofman, Declan G. Murphy, Paul J. Neeson","doi":"10.1038/s41585-024-00913-8","DOIUrl":"10.1038/s41585-024-00913-8","url":null,"abstract":"High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer. Lutetium PSMA is approved for the treatment of advanced prostate cancer and is being studied in a neoadjuvant setting. The influence of lutetium PSMA on the tumour immune microenvironment is unknown. In selected patients, lutetium PSMA could be used as a stand-alone treatment or in combination with immunotherapy to produce long-lasting antitumour immunity.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"676-686"},"PeriodicalIF":12.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1038/s41585-024-00912-9
Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari
Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be ‘friends’ rather than ‘foes’ in prostate cancer treatment.
{"title":"From foes to friends: rethinking the role of lymph nodes in prostate cancer","authors":"Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari","doi":"10.1038/s41585-024-00912-9","DOIUrl":"10.1038/s41585-024-00912-9","url":null,"abstract":"Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be ‘friends’ rather than ‘foes’ in prostate cancer treatment.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"687-700"},"PeriodicalIF":12.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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