MP14-07 DEVELOPMENT OF A LIQUID BIOPSY USING EXTRACELLULAR VESICLES TO ASSESS THE SYSTEMIC T CELL IMMUNE LANDSCAPE IN BLADDER CANCER

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP14-07 DEVELOPMENT OF A LIQUID BIOPSY USING EXTRACELLULAR VESICLES TO ASSESS THE SYSTEMIC T CELL IMMUNE LANDSCAPE IN BLADDER CANCER Karen Doersch, Samuel Walker, Thomas Osinski, Jonathan Flax, and James McGrath Karen DoerschKaren Doersch More articles by this author , Samuel WalkerSamuel Walker More articles by this author , Thomas OsinskiThomas Osinski More articles by this author , Jonathan FlaxJonathan Flax More articles by this author , and James McGrathJames McGrath More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urothelial carcinoma (UC) is commonly treated with therapeutics that target the immune system, such as checkpoint immunotherapy or Bacillus Calmette-Guerin (BCG). While assessment of T cell function is of utility in predicting response to these therapies, current methods for evaluating systemic T cell immunity or intratumoral immune behavior are limited. As antigenically activated T cells produce extracellular vesicles (EVs) carrying markers of cell subtype and activation state and these are found in the blood, we hypothesized that serum T cell derived EVs could be used to interrogate the systemic antitumor T cell response. The purpose of this study was to evaluate a novel microfluidic strategy ‘catch and display for liquid biopsy’ [CAD-LB] for the rapid assessment of T cell biomarkers on individual EVs from T cell conditioned medium or blood. METHODS: T cell derived EVs from cultured cells. We hypothesized that T cell derived EVs have markers of T cell function that mirror their cell of origin. To test this, we assessed markers of activation and exhaustion on EVs secreted by T cells. Activation and exhaustion were induced in vitro by stimulation with anti-CD3/CD28 beads, mimicking the in vivo stimulation of T cells in an antigen-rich tumor environment. T cell subtype and activation state were assessed by CAD-LB and flow cytometry. T cell markers on serum EVs. We developed an affinity purification method for CD3+ EVs and subsequently evaluated the level of T cell biomarkers on these using CAD-LB in UC specimens from patients. RESULTS: 1. T cell marker expression on EVs from conditioned medium from resting, activated and exhausted cells followed the pattern present on the EV producing T cells. 2. T cell derived EVs from UC patient serum identified markers of activated and functionally exhausted cells, indicating that we can capture the full range of T cell functionality with CAD-LB. 3. Detected T cell EVs with markers of non-circulating tissue-resident cells (present in tumor, secondary lymphoid and peripheral tissue) demonstrate that EVs capture the systemic immune responses. CONCLUSIONS: T cell derived EVs capture the phenotype and identity of their cell of origin. CAD-LB detects a range of T cell populations in serum. Future work will test if T cell EVs capture tumor and systemic antitumor immunity, which may help identify UC patients more likely to respond to immunotherapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e184 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karen Doersch More articles by this author Samuel Walker More articles by this author Thomas Osinski More articles by this author Jonathan Flax More articles by this author James McGrath More articles by this author Expand All Advertisement PDF downloadLoading ...