MP08-01 IMMUNOSUPPRESSIVE MECHANISMS OF INTEGRIN BETA8 FOR IMMUNE RESPONSE INDUCED BY BCG THERAPY

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP08-01 IMMUNOSUPPRESSIVE MECHANISMS OF INTEGRIN BETA8 FOR IMMUNE RESPONSE INDUCED BY BCG THERAPY Seiji Hoshi, Hiroki Natsuya, Yuki Harigane, Kei Yaginuma, Syunta Makabe, Yuki Yoshida, Satoru Meguro, Akifumi Onagi, Kanako Matsuoka, Tomoyuki Koguchi, Junya Hata, Yuichi Sato, Hidenori Akaihata, Masao Kataoka, Soichiro Ogawa, Motohide Uemura, and Yoshiyuki Kojima Seiji HoshiSeiji Hoshi More articles by this author , Hiroki NatsuyaHiroki Natsuya More articles by this author , Yuki HariganeYuki Harigane More articles by this author , Kei YaginumaKei Yaginuma More articles by this author , Syunta MakabeSyunta Makabe More articles by this author , Yuki YoshidaYuki Yoshida More articles by this author , Satoru MeguroSatoru Meguro More articles by this author , Akifumi OnagiAkifumi Onagi More articles by this author , Kanako MatsuokaKanako Matsuoka More articles by this author , Tomoyuki KoguchiTomoyuki Koguchi More articles by this author , Junya HataJunya Hata More articles by this author , Yuichi SatoYuichi Sato More articles by this author , Hidenori AkaihataHidenori Akaihata More articles by this author , Masao KataokaMasao Kataoka More articles by this author , Soichiro OgawaSoichiro Ogawa More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , and Yoshiyuki KojimaYoshiyuki Kojima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In non-muscle invasive bladder cancer (NMIBC), immunosuppressive factors responsible for post-BCG therapy recurrence remains unclear. In this study, we performed comprehensive genetic analysis and functional analysis in untreated NMIBC to explore key players of immunosuppression associated with recurrence after BCG therapy. METHODS: 13 patients (73.5±8.9 years old) with untreated NMIBC who were treated over 6 months BCG and could be followed up for 5 years were included. They were divided into two groups; recurrence (n=6) and non-recurrence groups (n=7). Genes that are upregulated in bladder cancer tissues compared to normal bladder tissues and associated with recurrence and immunosuppression were extracted from the microarray of untreated bladder cancer tissue. In bladder cancer cells (RT4 and UMUC5), the expression of the genes was evaluated by qPCR and Western blot (WB). Cell proliferation (WST assay), adhesion (CytoSelectTM), invasion (scratch assay) and secretion of immunosuppressive cytokine TGF-β1 (ELISA and immunostaining) were also assessed after knockdown of the genes to evaluate the function of the gene in bladder cancer cells. RESULTS: Microarray analysis revealed integrin beta 8 (ITGB8) was significantly upregulated in the recurrence group (p<0.0001). The microarray results were validated with ITGB8 immunostaining of the same patient's tissue and showed similar results to the microarray. qPCR and WB results showed that ITGB8 was highly expressed in UMUC5 compared to RT4. In UMUC5, ITGB8 knockdown significantly decreased cell proliferation, adhesion, invasion (p<0.01) and TGF-β1 secretion (p<0.01). It also significantly reduced staining for TGF-β1 and TGF-β1 LAP-D, which indicates TGF-β1 activation (p<0.01). CONCLUSIONS: In untreated NMIBC, ITGB8 may contribute to recurrence after BCG by suppressing tumor immunity through the activation of TGF-β1. Thus, inhibition of ITGB8 was considered to prevent the recurrence of NMIBC via inducing an immune response by BCG therapy. Source of Funding: This study was supported by a Grant-in-Aid for Young Investigators from the Japan Society for Promotion of Science (JSPS KAKENHI 19K18590, S. Hoshi) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e93 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seiji Hoshi More articles by this author Hiroki Natsuya More articles by this author Yuki Harigane More articles by this author Kei Yaginuma More articles by this author Syunta Makabe More articles by this author Yuki Yoshida More articles by this author Satoru Meguro More articles by this author Akifumi Onagi More articles by this author Kanako Matsuoka More articles by this author Tomoyuki Koguchi More articles by this author Junya Hata More articles by this author Yuichi Sato More articles by this author Hidenori Akaihata More articles by this author Masao Kataoka More articles by this author Soichiro Ogawa More articles by this author Motohide Uemura More articles by this author Yoshiyuki Kojima More articles by this author Expand All Advertisement PDF downloadLoading ...