PD42-03 HIGH LEVELS OF BASELINE IGG1, IGG3, AND IFN-G MAY BE ASSOCIATED WITH RESISTANCE TO BCG THERAPY FOR TREATMENT OF NMIBC

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (PD42)1 Sep 2021PD42-03 HIGH LEVELS OF BASELINE IGG1, IGG3, AND IFN-G MAY BE ASSOCIATED WITH RESISTANCE TO BCG THERAPY FOR TREATMENT OF NMIBC Jorge Daza, Yuanshuo Wang, Andrew Charap, Berengere Salome, Rachel Brody, Emilie Grasset, Giuliana Magri, Dominic LaRoche, Yong Lee, Rafael Cabal, Adam Farkas, Li Wang, Jun Zhu, Kristin Beaumont, Ketan Badani, Reza Mehrazin, Peter Wiklund, Robert Sebra, Matthew Galsky, Nina Bharwadj, Amir Horowitz, and John Sfakianos Jorge DazaJorge Daza More articles by this author , Yuanshuo WangYuanshuo Wang More articles by this author , Andrew CharapAndrew Charap More articles by this author , Berengere SalomeBerengere Salome More articles by this author , Rachel BrodyRachel Brody More articles by this author , Emilie GrassetEmilie Grasset More articles by this author , Giuliana MagriGiuliana Magri More articles by this author , Dominic LaRocheDominic LaRoche More articles by this author , Yong LeeYong Lee More articles by this author , Rafael CabalRafael Cabal More articles by this author , Adam FarkasAdam Farkas More articles by this author , Li WangLi Wang More articles by this author , Jun ZhuJun Zhu More articles by this author , Kristin BeaumontKristin Beaumont More articles by this author , Ketan BadaniKetan Badani More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , Peter WiklundPeter Wiklund More articles by this author , Robert SebraRobert Sebra More articles by this author , Matthew GalskyMatthew Galsky More articles by this author , Nina BharwadjNina Bharwadj More articles by this author , Amir HorowitzAmir Horowitz More articles by this author , and John SfakianosJohn Sfakianos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002056.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The mechanisms that contribute to protection from tumor recurrence after M.Bovis BCG are not fully elucidated. We aim to evaluate the role of Antibody Dependent Cell Cytotoxicity (ADCC) in BCG therapy for NMIBC. METHODS: Formalin-fixed and paraffin-embedded (FFPE) tissue sections before and after BCG therapy were used for bulk targeted gene expression analysis. Differential gene expression analysis was performed on targeted RNAseq data. Gene Set Enrichment Analysis (GSEA) was performed using the “Hallmark Gene Sets” from the Broad Intitute’s Molecular Signatures Database (MSigDB) and customized assembled gene sets. Enzyme linked immunosorbent assay (ELISA) and OLink Proteomics® inflammation panel were used to profile IgG1/3, and Interferon Gamma (IFN-g), respectively on prospectively collected plasma from BCG-treated patients (N=14) at specific timepoints throughout the treatment. RESULTS: B cell markers and IFN-g signatures were the two most enriched pathways after BCG therapy in the GSEA (Fig. 1A). We also observed significantly increased gene expression of IgG1 and IgG3 after BCG therapy (Fig. 1B), which may induce ADCC reactivity via FcgRIIIA signaling. In non-recurrent cases, we observed an increase in plasma IgG1/3 concentration that preceded IFN-g hyperactivity after 1st and 3rd BCG doses (Fig. 2). In contrast, patients that recur after BCG therapy had higher levels of plasma IFN-g at baseline, which remained elevated throughout the induction phase unrelated to IgG1/3 concentrations (Fig. 2). While the median recurrence time was 3.9 months, the median follow-up for non-recurrent patients was 36.7 months. CONCLUSIONS: We observed increased expression of B cell-related genes and an IFN-g signature after BCG therapy. Moreover, we found that response to BCG may include activation of Immune cells through IgG1/IgG3-mediated ADCC reactivity. Future studies in larger patient cohorts should measure IFN-g during BCG therapy and consider a role for ADCC in mediating protection from tumor recurrence BCG therapy. Source of Funding: Self-funded © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e725-e725 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jorge Daza More articles by this author Yuanshuo Wang More articles by this author Andrew Charap More articles by this author Berengere Salome More articles by this author Rachel Brody More articles by this author Emilie Grasset More articles by this author Giuliana Magri More articles by this author Dominic LaRoche More articles by this author Yong Lee More articles by this author Rafael Cabal More articles by this author Adam Farkas More articles by this author Li Wang More articles by this author Jun Zhu More articles by this author Kristin Beaumont More articles by this author Ketan Badani More articles by this author Reza Mehrazin More articles by this author Peter Wiklund More articles by this author Robert Sebra More articles by this author Matthew Galsky More articles by this author Nina Bharwadj More articles by this author Amir Horowitz More articles by this author John Sfakianos More articles by this author Expand All Advertisement Loading ...