Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti-tumour T-cell activation - IRE-IMMUNO study.

Autor:	Geboers B; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia.; Department of Urology, St. Vincent's Private Clinic, Sydney, New South Wales, Australia.; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.; Cancer Centre Amsterdam, Amsterdam, The Netherlands., Scheltema MJ; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia.; Department of Urology, St. Antonius Hospital, Utrecht, The Netherlands., Jung J; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Bakker J; Department of Medical Oncology, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.; Cancer Centre Amsterdam, Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands., Timmer FEF; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.; Cancer Centre Amsterdam, Amsterdam, The Netherlands., Cerutti X; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Katelaris A; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Doan P; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Gondoputro W; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Blazevski A; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Agrawal S; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Matthews J; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia.; Department of Urology, St. Vincent's Private Clinic, Sydney, New South Wales, Australia., Haynes AM; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia., Robertson T; Department of Anesthesiology, St. Vincent's Private Clinic, Sydney, New South Wales, Australia., Thompson JE; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia.; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia., Meijerink MR; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.; Cancer Centre Amsterdam, Amsterdam, The Netherlands., Clark SJ; Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Sydney, New South Wales, Australia., de Gruijl TD; Department of Medical Oncology, Amsterdam UMC, Location Vrije Universiteit, Amsterdam, The Netherlands.; Cancer Centre Amsterdam, Amsterdam, The Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands., Stricker PD; St. Vincent's Prostate Cancer Research Centre, Sydney, New South Wales, Australia.; Department of Urology, St. Vincent's Private Clinic, Sydney, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	BJU international [BJU Int] 2024 Aug 05. Date of Electronic Publication: 2024 Aug 05.
DOI:	10.1111/bju.16496
Abstrakt:	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. (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text