MP70-19 SIGNIFICANTLY HIGH LEVELS OF ACTIVATED CYTOTOXIC T-LYMPHOCYTES ARE FOUND IN BOTH BENIGN AND MALIGNANT PROSTATE TISSUES

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2018MP70-19 SIGNIFICANTLY HIGH LEVELS OF ACTIVATED CYTOTOXIC T-LYMPHOCYTES ARE FOUND IN BOTH BENIGN AND MALIGNANT PROSTATE TISSUES Dixon T.S. Woon, Genevieve Whitty, Weranja K.B. Ranasinghe, Manvendra Saxena, Damien Bolton, and Ian Davis Dixon T.S. WoonDixon T.S. Woon More articles by this author , Genevieve WhittyGenevieve Whitty More articles by this author , Weranja K.B. RanasingheWeranja K.B. Ranasinghe More articles by this author , Manvendra SaxenaManvendra Saxena More articles by this author , Damien BoltonDamien Bolton More articles by this author , and Ian DavisIan Davis More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2263AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Studies have confirmed that some tumours can resist immune cells infiltration and escape immune elimination. That leads to the suggestion of categorizing tumours into T cell-inflamed or non-T cell-inflamed phenotypes. T cell-inflamed tumours are infiltrated by T cells, but they can resist immune elimination by manipulating the inhibitory effects of immune suppressive pathways (e.g. CTLA4, PD-1). The non T cell-inflamed tumours resist immune attack by T cells exclusion, via the activation of oncological pathways (e.g.Wnt/β-catenin). In some immunotherapy trials (CTLA inhibitor, PD-1 inhibitors), patients with the most clinical response are those with the T cell-inflamed tumour phenotype. We aim to determine which phenotype prostate cancer (PC) is, by characterizing the proportion of cytotoxic lymphocytes (CTL) in PC and their activation status. Benign prostatic hyperplasia (BPH) and normal prostate (NP) tissues were collected for comparison. METHODS Fresh BPH, NP, and PC tissues were processed and studied as single cell suspensions. Peripheral blood mononuclear cells (PBMC) of patients were isolated with Ficoll separation technique. Using flow-cytometry, the proportion of CTL in the CD45 subset (CD8+/CD45+) and their activation status (CD45, CD8, CD69+ T cells) were evaluated first; and then compared with their matching PBMC. RESULTS 28 patients were recruited. The mean percentages of CTL in the CD45+ subset in tissues for patients with BPH (n=4), NP (n=5), and PC (n=19) were 27.2, 35,4 and 24.7 respectively (no statistically significant difference). The CTL Tissue/PBMC ratios were 1.8, 2.0, and 1.1 respectively (NP vs PC; p-value of 0.029). The mean percentages of activated CTL in tissues for patients with BPH, NP, and PC were 79.1%, 75.4%, and 68.8 respectively; with an activated CTL Tissue/PBMC ratio of 18.0, 23.6 and 22.4 respectively (no statistically significant difference). Two BPH and one NP samples had prostatitis while two NP patients had intra-vesical BCG previously. CONCLUSIONS This study shows that there are TILs in PC tissues and the levels are the same as in peripheral blood. A significant percentage of CTL in PC tissues are activated, and the levels are 22 times higher than blood. This confirms that PC is of the T cell-inflamed phenotype tumour and should, therefore, respond to immune check-point immunotherapy. In BPH and NP, the CTL and the activated CTL levels in tissues are 2x and 20x higher than blood. This may be secondary to prostatitis, previous BCG therapy, or other pro-inflammatory conditions. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e941-e942 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Dixon T.S. Woon More articles by this author Genevieve Whitty More articles by this author Weranja K.B. Ranasinghe More articles by this author Manvendra Saxena More articles by this author Damien Bolton More articles by this author Ian Davis More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...