Mp69-20 characterizing the immune phenotype of fgfr3 mutated upper tract urothelial carcinoma (utuc) using single-cell (sc)rna-sequencing (seq)

You have accessJournal of UrologyCME1 Apr 2023MP69-20 CHARACTERIZING THE IMMUNE PHENOTYPE OF FGFR3 MUTATED UPPER TRACT UROTHELIAL CARCINOMA (UTUC) USING SINGLE-CELL (SC)RNA-SEQUENCING (SEQ) Andrew B. Katims, Fengshen Kuo, Peter A. Reisz, Andrew Tracey, Jasmine Thomas, Wesley Yip, Bernard H. Bochner, Eugene J. Pietzak, David B. Solit, A. Ari Hakimi, Taha Merghoub, Kwanghee Kim, and Jonathan A. Coleman Andrew B. KatimsAndrew B. Katims More articles by this author , Fengshen KuoFengshen Kuo More articles by this author , Peter A. ReiszPeter A. Reisz More articles by this author , Andrew TraceyAndrew Tracey More articles by this author , Jasmine ThomasJasmine Thomas More articles by this author , Wesley YipWesley Yip More articles by this author , Bernard H. BochnerBernard H. Bochner More articles by this author , Eugene J. PietzakEugene J. Pietzak More articles by this author , David B. SolitDavid B. Solit More articles by this author , A. Ari HakimiA. Ari Hakimi More articles by this author , Taha MerghoubTaha Merghoub More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , and Jonathan A. ColemanJonathan A. Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: FGFR3 is the most common mutation in UTUC. Tumors harboring FGFR3 mutations (FGFR3-M) have a T-cell impaired tumor microenvironment which may explain the poor response to immune checkpoint blockade. We performed scRNA-seq on 7 tumors to further characterize the T-cell immune phenotype of FGFR3-M tumors. METHODS: scRNA-seq was performed on 7 UTUC tissue specimens from 7 patients who were treatment naïve using an established institutional process. We performed targeted gene sequencing on all samples to identify mutational calls. We assessed the phenotype of defined cell clusters and the immune composition of each sample according to known marker gene expression and SingleR prediction. Gene set enrichment analysis was performed over the differentially expressed genes with the Gene Ontology Biologic Process. RESULTS: We identified 19 immune cell clusters (8 T-cell clusters) with unique biologic function (Figure 1). Within the CD4 compartment, FGFR3-M was enriched with exhausted/active CD4 cells characterized with Th17 cell differentiation/immune regulatory function (cluster 4) and yet with lower frequency of naive-like CD4 cells possessing alpha-beta T cell activation functions and lower T-cell receptor signaling (cluster 2). Regulatory T cells (cluster 5) were less frequently found in FGFR3-M tumors compared to their wild-type counterpart. In the CD8 compartment, FGFR3-M tumors had higher infiltration in cluster 3 which corresponds to a naïve state with lower exhausted/active markers, lower cytotoxic activity, leukocyte apoptotic process, and alpha-beta T cell differentiation regulation. There was also a lower proportion among cluster 9, a mixture of NK and CD8 cytotoxic cells, which is characterized by high cytotoxic activity, lower exhausted/active markers and response to interleukin (IL)-1, tumor necrosis factor (TNF), and NK cell chemotaxis. CONCLUSIONS: FGFR3 mutated patients have a T-cell phenotype with more active/exhausted Th17-like CD4, lower Treg, and more CD8/cytotoxic cells in naïve state with lower response to IL-1 and TNF. scRNA-seq revealed enrichment of different functional states among T-cell compartments which may lead to improved therapeutic options in the future. Source of Funding: Department of Defense, The Thompson Family Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e972 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew B. Katims More articles by this author Fengshen Kuo More articles by this author Peter A. Reisz More articles by this author Andrew Tracey More articles by this author Jasmine Thomas More articles by this author Wesley Yip More articles by this author Bernard H. Bochner More articles by this author Eugene J. Pietzak More articles by this author David B. Solit More articles by this author A. Ari Hakimi More articles by this author Taha Merghoub More articles by this author Kwanghee Kim More articles by this author Jonathan A. Coleman More articles by this author Expand All Advertisement PDF downloadLoading ...