Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study
Objectives To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa). Patients and Methods Between February 2021 and June 2022, before...
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| Veröffentlicht in: | BJU international 2025-02, Vol.135 (2), p.319-328 |
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| creator | Geboers, Bart Scheltema, Matthijs J. Jung, Jason Bakker, Joyce Timmer, Florentine E.F. Cerutti, Xanthe Katelaris, Athos Doan, Paul Gondoputro, William Blazevski, Alexandar Agrawal, Shikha Matthews, Jayne Haynes, Anne‐Maree Robertson, Tim Thompson, James E. Meijerink, Martijn R. Clark, Susan J. Gruijl, Tanja D. Stricker, Phillip D. |
| description | Objectives
To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa).
Patients and Methods
Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2–3, clinical cancer stage ≤T2c, prostate‐specific antigen level |
| doi_str_mv | 10.1111/bju.16496 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_3088563584</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3157255793</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3346-737bbab4cdad887b713eb9c907709424474f37e6cbe5bd3e553ce4549930aec83</originalsourceid><addsrcrecordid>eNp1kktuFDEQhlsIREJgwQWQJTawmMSO7XZ7hSAKMCghEspI7Cy3uyZ41G13_JhodjkCEhfImmPkKDkJHiaJAAlvXKr6_FeVq6rqOcG7pJy9dpF3Sc1k_aDaJqxmE0bw14d3Npb1VvUkxgXGxVHzx9UWlQSTmsrt6uc0BFhCiLbtAUEPJgU_-qCT9Q75Oeq90b2N0KEx-Jh0AmS0MxCurzp_4QKc5b44I7LDkB2gmMcxQIzr59p111fWddmUeFzFBIM1xZvszeX3lAefAzotpoG-R9oku9ykvbn8gaZfDktkenw8-3yCYsrd6mn1aK77CM9u751q9v7w9ODj5Ojkw_Tg7dHEUMrqiaCibXXLTKe7phGtIBRaaSQWAku2z5hgcyqgNi3wtqPAOTXAOJOSYg2moTvVm43umNsBOgMuBd2rMdhBh5Xy2qq_I85-U2d-qQgRjMtGFoVXtwrBn2eISQ02rpvUDnyOiuKm4TXlDSvoy3_QRfkVV_pTlHCxz7mQtFCvN5QpM4gB5vfVEKzWK6DKCqjfK1DYF3-Wf0_ezbwAexvgwvaw-r-SevdptpH8BRG9xf4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3157255793</pqid></control><display><type>article</type><title>Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Geboers, Bart ; Scheltema, Matthijs J. ; Jung, Jason ; Bakker, Joyce ; Timmer, Florentine E.F. ; Cerutti, Xanthe ; Katelaris, Athos ; Doan, Paul ; Gondoputro, William ; Blazevski, Alexandar ; Agrawal, Shikha ; Matthews, Jayne ; Haynes, Anne‐Maree ; Robertson, Tim ; Thompson, James E. ; Meijerink, Martijn R. ; Clark, Susan J. ; Gruijl, Tanja D. ; Stricker, Phillip D.</creator><creatorcontrib>Geboers, Bart ; Scheltema, Matthijs J. ; Jung, Jason ; Bakker, Joyce ; Timmer, Florentine E.F. ; Cerutti, Xanthe ; Katelaris, Athos ; Doan, Paul ; Gondoputro, William ; Blazevski, Alexandar ; Agrawal, Shikha ; Matthews, Jayne ; Haynes, Anne‐Maree ; Robertson, Tim ; Thompson, James E. ; Meijerink, Martijn R. ; Clark, Susan J. ; Gruijl, Tanja D. ; Stricker, Phillip D.</creatorcontrib><description>Objectives
To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa).
Patients and Methods
Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2–3, clinical cancer stage ≤T2c, prostate‐specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa‐specific T‐cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY‐ESO‐1]) were determined by interferon‐γ enzyme‐linked immunospot assay (ELISpot). Repeated‐measures analysis of variance and two‐sided Student's t‐tests were used to compare immune responses over time and between treatment cohorts.
Results
Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T‐lymphocyte antigen 4 (CTLA‐4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T‐cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY‐ESO‐1 specific T‐cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP.
Conclusions
Irreversible electroporation induces a PCa‐specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA‐4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high‐risk localised or (oligo)metastatic disease.</description><identifier>ISSN: 1464-4096</identifier><identifier>ISSN: 1464-410X</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/bju.16496</identifier><identifier>PMID: 39101639</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>ablation ; abscopal effect ; Acid phosphatase ; Aged ; Antigens ; CD8 antigen ; Cell activation ; Cytotoxicity ; Down-Regulation ; Effector cells ; Electroporation ; Electroporation - methods ; Enzyme-linked immunosorbent assay ; Esophageal cancer ; Esophageal carcinoma ; Flow cytometry ; focal therapy ; Humans ; immune response ; Immunoregulation ; Immunosuppression ; immunotherapy ; irreversible electroporation ; Lymphocyte Activation - immunology ; Lymphocytes T ; Male ; Metastases ; Middle Aged ; Original ; Patients ; Peripheral blood ; Prospective Studies ; Prostate cancer ; Prostatectomy ; Prostatectomy - methods ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - surgery ; Squamous cell carcinoma ; T-Lymphocytes - immunology ; Tumor microenvironment ; Tumors</subject><ispartof>BJU international, 2025-02, Vol.135 (2), p.319-328</ispartof><rights>2024 The Author(s). published by John Wiley & Sons Ltd on behalf of BJU International.</rights><rights>2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3346-737bbab4cdad887b713eb9c907709424474f37e6cbe5bd3e553ce4549930aec83</cites><orcidid>0000-0002-5115-9930 ; 0000-0003-4946-7982 ; 0000-0002-9098-9574 ; 0000-0002-8137-9299 ; 0000-0002-0934-0656</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbju.16496$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbju.16496$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39101639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geboers, Bart</creatorcontrib><creatorcontrib>Scheltema, Matthijs J.</creatorcontrib><creatorcontrib>Jung, Jason</creatorcontrib><creatorcontrib>Bakker, Joyce</creatorcontrib><creatorcontrib>Timmer, Florentine E.F.</creatorcontrib><creatorcontrib>Cerutti, Xanthe</creatorcontrib><creatorcontrib>Katelaris, Athos</creatorcontrib><creatorcontrib>Doan, Paul</creatorcontrib><creatorcontrib>Gondoputro, William</creatorcontrib><creatorcontrib>Blazevski, Alexandar</creatorcontrib><creatorcontrib>Agrawal, Shikha</creatorcontrib><creatorcontrib>Matthews, Jayne</creatorcontrib><creatorcontrib>Haynes, Anne‐Maree</creatorcontrib><creatorcontrib>Robertson, Tim</creatorcontrib><creatorcontrib>Thompson, James E.</creatorcontrib><creatorcontrib>Meijerink, Martijn R.</creatorcontrib><creatorcontrib>Clark, Susan J.</creatorcontrib><creatorcontrib>Gruijl, Tanja D.</creatorcontrib><creatorcontrib>Stricker, Phillip D.</creatorcontrib><title>Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>Objectives
To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa).
Patients and Methods
Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2–3, clinical cancer stage ≤T2c, prostate‐specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa‐specific T‐cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY‐ESO‐1]) were determined by interferon‐γ enzyme‐linked immunospot assay (ELISpot). Repeated‐measures analysis of variance and two‐sided Student's t‐tests were used to compare immune responses over time and between treatment cohorts.
Results
Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T‐lymphocyte antigen 4 (CTLA‐4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T‐cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY‐ESO‐1 specific T‐cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP.
Conclusions
Irreversible electroporation induces a PCa‐specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA‐4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high‐risk localised or (oligo)metastatic disease.</description><subject>ablation</subject><subject>abscopal effect</subject><subject>Acid phosphatase</subject><subject>Aged</subject><subject>Antigens</subject><subject>CD8 antigen</subject><subject>Cell activation</subject><subject>Cytotoxicity</subject><subject>Down-Regulation</subject><subject>Effector cells</subject><subject>Electroporation</subject><subject>Electroporation - methods</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Esophageal cancer</subject><subject>Esophageal carcinoma</subject><subject>Flow cytometry</subject><subject>focal therapy</subject><subject>Humans</subject><subject>immune response</subject><subject>Immunoregulation</subject><subject>Immunosuppression</subject><subject>immunotherapy</subject><subject>irreversible electroporation</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Prospective Studies</subject><subject>Prostate cancer</subject><subject>Prostatectomy</subject><subject>Prostatectomy - methods</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - surgery</subject><subject>Squamous cell carcinoma</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>1464-4096</issn><issn>1464-410X</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kktuFDEQhlsIREJgwQWQJTawmMSO7XZ7hSAKMCghEspI7Cy3uyZ41G13_JhodjkCEhfImmPkKDkJHiaJAAlvXKr6_FeVq6rqOcG7pJy9dpF3Sc1k_aDaJqxmE0bw14d3Npb1VvUkxgXGxVHzx9UWlQSTmsrt6uc0BFhCiLbtAUEPJgU_-qCT9Q75Oeq90b2N0KEx-Jh0AmS0MxCurzp_4QKc5b44I7LDkB2gmMcxQIzr59p111fWddmUeFzFBIM1xZvszeX3lAefAzotpoG-R9oku9ykvbn8gaZfDktkenw8-3yCYsrd6mn1aK77CM9u751q9v7w9ODj5Ojkw_Tg7dHEUMrqiaCibXXLTKe7phGtIBRaaSQWAku2z5hgcyqgNi3wtqPAOTXAOJOSYg2moTvVm43umNsBOgMuBd2rMdhBh5Xy2qq_I85-U2d-qQgRjMtGFoVXtwrBn2eISQ02rpvUDnyOiuKm4TXlDSvoy3_QRfkVV_pTlHCxz7mQtFCvN5QpM4gB5vfVEKzWK6DKCqjfK1DYF3-Wf0_ezbwAexvgwvaw-r-SevdptpH8BRG9xf4</recordid><startdate>202502</startdate><enddate>202502</enddate><creator>Geboers, Bart</creator><creator>Scheltema, Matthijs J.</creator><creator>Jung, Jason</creator><creator>Bakker, Joyce</creator><creator>Timmer, Florentine E.F.</creator><creator>Cerutti, Xanthe</creator><creator>Katelaris, Athos</creator><creator>Doan, Paul</creator><creator>Gondoputro, William</creator><creator>Blazevski, Alexandar</creator><creator>Agrawal, Shikha</creator><creator>Matthews, Jayne</creator><creator>Haynes, Anne‐Maree</creator><creator>Robertson, Tim</creator><creator>Thompson, James E.</creator><creator>Meijerink, Martijn R.</creator><creator>Clark, Susan J.</creator><creator>Gruijl, Tanja D.</creator><creator>Stricker, Phillip D.</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5115-9930</orcidid><orcidid>https://orcid.org/0000-0003-4946-7982</orcidid><orcidid>https://orcid.org/0000-0002-9098-9574</orcidid><orcidid>https://orcid.org/0000-0002-8137-9299</orcidid><orcidid>https://orcid.org/0000-0002-0934-0656</orcidid></search><sort><creationdate>202502</creationdate><title>Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study</title><author>Geboers, Bart ; Scheltema, Matthijs J. ; Jung, Jason ; Bakker, Joyce ; Timmer, Florentine E.F. ; Cerutti, Xanthe ; Katelaris, Athos ; Doan, Paul ; Gondoputro, William ; Blazevski, Alexandar ; Agrawal, Shikha ; Matthews, Jayne ; Haynes, Anne‐Maree ; Robertson, Tim ; Thompson, James E. ; Meijerink, Martijn R. ; Clark, Susan J. ; Gruijl, Tanja D. ; Stricker, Phillip D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3346-737bbab4cdad887b713eb9c907709424474f37e6cbe5bd3e553ce4549930aec83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>ablation</topic><topic>abscopal effect</topic><topic>Acid phosphatase</topic><topic>Aged</topic><topic>Antigens</topic><topic>CD8 antigen</topic><topic>Cell activation</topic><topic>Cytotoxicity</topic><topic>Down-Regulation</topic><topic>Effector cells</topic><topic>Electroporation</topic><topic>Electroporation - methods</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Esophageal cancer</topic><topic>Esophageal carcinoma</topic><topic>Flow cytometry</topic><topic>focal therapy</topic><topic>Humans</topic><topic>immune response</topic><topic>Immunoregulation</topic><topic>Immunosuppression</topic><topic>immunotherapy</topic><topic>irreversible electroporation</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Prospective Studies</topic><topic>Prostate cancer</topic><topic>Prostatectomy</topic><topic>Prostatectomy - methods</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - surgery</topic><topic>Squamous cell carcinoma</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geboers, Bart</creatorcontrib><creatorcontrib>Scheltema, Matthijs J.</creatorcontrib><creatorcontrib>Jung, Jason</creatorcontrib><creatorcontrib>Bakker, Joyce</creatorcontrib><creatorcontrib>Timmer, Florentine E.F.</creatorcontrib><creatorcontrib>Cerutti, Xanthe</creatorcontrib><creatorcontrib>Katelaris, Athos</creatorcontrib><creatorcontrib>Doan, Paul</creatorcontrib><creatorcontrib>Gondoputro, William</creatorcontrib><creatorcontrib>Blazevski, Alexandar</creatorcontrib><creatorcontrib>Agrawal, Shikha</creatorcontrib><creatorcontrib>Matthews, Jayne</creatorcontrib><creatorcontrib>Haynes, Anne‐Maree</creatorcontrib><creatorcontrib>Robertson, Tim</creatorcontrib><creatorcontrib>Thompson, James E.</creatorcontrib><creatorcontrib>Meijerink, Martijn R.</creatorcontrib><creatorcontrib>Clark, Susan J.</creatorcontrib><creatorcontrib>Gruijl, Tanja D.</creatorcontrib><creatorcontrib>Stricker, Phillip D.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Geboers, Bart</au><au>Scheltema, Matthijs J.</au><au>Jung, Jason</au><au>Bakker, Joyce</au><au>Timmer, Florentine E.F.</au><au>Cerutti, Xanthe</au><au>Katelaris, Athos</au><au>Doan, Paul</au><au>Gondoputro, William</au><au>Blazevski, Alexandar</au><au>Agrawal, Shikha</au><au>Matthews, Jayne</au><au>Haynes, Anne‐Maree</au><au>Robertson, Tim</au><au>Thompson, James E.</au><au>Meijerink, Martijn R.</au><au>Clark, Susan J.</au><au>Gruijl, Tanja D.</au><au>Stricker, Phillip D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2025-02</date><risdate>2025</risdate><volume>135</volume><issue>2</issue><spage>319</spage><epage>328</epage><pages>319-328</pages><issn>1464-4096</issn><issn>1464-410X</issn><eissn>1464-410X</eissn><abstract>Objectives
To prospectively compare systemic anti‐tumour immune responses induced by irreversible electroporation (IRE) and robot‐assisted radical prostatectomy (RARP) in patients with localised intermediate‐risk prostate cancer (PCa).
Patients and Methods
Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2–3, clinical cancer stage ≤T2c, prostate‐specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa‐specific T‐cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY‐ESO‐1]) were determined by interferon‐γ enzyme‐linked immunospot assay (ELISpot). Repeated‐measures analysis of variance and two‐sided Student's t‐tests were used to compare immune responses over time and between treatment cohorts.
Results
Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T‐lymphocyte antigen 4 (CTLA‐4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T‐cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY‐ESO‐1 specific T‐cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP.
Conclusions
Irreversible electroporation induces a PCa‐specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA‐4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high‐risk localised or (oligo)metastatic disease.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39101639</pmid><doi>10.1111/bju.16496</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5115-9930</orcidid><orcidid>https://orcid.org/0000-0003-4946-7982</orcidid><orcidid>https://orcid.org/0000-0002-9098-9574</orcidid><orcidid>https://orcid.org/0000-0002-8137-9299</orcidid><orcidid>https://orcid.org/0000-0002-0934-0656</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1464-4096 |
| ispartof | BJU international, 2025-02, Vol.135 (2), p.319-328 |
| issn | 1464-4096 1464-410X 1464-410X |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | ablation abscopal effect Acid phosphatase Aged Antigens CD8 antigen Cell activation Cytotoxicity Down-Regulation Effector cells Electroporation Electroporation - methods Enzyme-linked immunosorbent assay Esophageal cancer Esophageal carcinoma Flow cytometry focal therapy Humans immune response Immunoregulation Immunosuppression immunotherapy irreversible electroporation Lymphocyte Activation - immunology Lymphocytes T Male Metastases Middle Aged Original Patients Peripheral blood Prospective Studies Prostate cancer Prostatectomy Prostatectomy - methods Prostatic Neoplasms - immunology Prostatic Neoplasms - pathology Prostatic Neoplasms - surgery Squamous cell carcinoma T-Lymphocytes - immunology Tumor microenvironment Tumors |
| title | Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti‐tumour T‐cell activation – IRE‐IMMUNO study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T15%3A40%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Irreversible%20electroporation%20of%20localised%20prostate%20cancer%C2%A0downregulates%20immune%20suppression%20and%C2%A0induces%20systemic%20anti%E2%80%90tumour%20T%E2%80%90cell%20activation%20%E2%80%93%20IRE%E2%80%90IMMUNO%20study&rft.jtitle=BJU%20international&rft.au=Geboers,%20Bart&rft.date=2025-02&rft.volume=135&rft.issue=2&rft.spage=319&rft.epage=328&rft.pages=319-328&rft.issn=1464-4096&rft.eissn=1464-410X&rft_id=info:doi/10.1111/bju.16496&rft_dat=%3Cproquest_pubme%3E3157255793%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3157255793&rft_id=info:pmid/39101639&rfr_iscdi=true |