MP48-02 SINGLE CELL RNA SEQUENCING OF UTUC IS FEASIBLE AND REVEALS HETEROGENEITY OF THE TUMOR AND IMMUNE MICROENVIRONMENT

Abstract

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP48)1 Sep 2021MP48-02 SINGLE CELL RNA SEQUENCING OF UTUC IS FEASIBLE AND REVEALS HETEROGENEITY OF THE TUMOR AND IMMUNE MICROENVIRONMENT Peter Reisz, Andrew Tracey, Fengshen Kuo, Jasmine Thomas, Quinlan Demac, Tim Clinton, Hong Truong, Andrew Lenis, Lucas Nogueira, Karan Nagar, Taha Merghoub, Bernard Bochner, Eugene Pietzak, David Solit, Kwanghee Kim, and Jonathan Coleman Peter ReiszPeter Reisz More articles by this author , Andrew TraceyAndrew Tracey More articles by this author , Fengshen KuoFengshen Kuo More articles by this author , Jasmine ThomasJasmine Thomas More articles by this author , Quinlan DemacQuinlan Demac More articles by this author , Tim ClintonTim Clinton More articles by this author , Hong TruongHong Truong More articles by this author , Andrew LenisAndrew Lenis More articles by this author , Lucas NogueiraLucas Nogueira More articles by this author , Karan NagarKaran Nagar More articles by this author , Taha MerghoubTaha Merghoub More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Eugene PietzakEugene Pietzak More articles by this author , David SolitDavid Solit More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002074.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) has unique clinical and molecular characteristics compared to bladder UC. Prior investigations have used bulk profiling of tumor tissue to identify molecular subtypes, classifying the majority of UTUC as luminal and T-cell depleted. Single-cell RNA sequencing (scRNA-seq) allows examination of intra-tumoral heterogeneity and the immune tumor microenvironment (TME). We applied scRNA-seq to better characterize UTUC. METHODS: scRNA-seq was performed on 16 UTUC tissue specimens using an established institutional process and the 10X Genomics platform. Sequencing reads were aligned/captured by 10X Cellranger, R/Seurat package. We assessed the composition of each specimen with known marker genes for molecular subtypes. We then assessed the composition of immune cells in each specimen using known marker genes. We compared high- (HG) and low-grade (LG) specimens by subtype composition and immune cell infiltrates. RESULTS: Table 1 describes cohort characteristics and sequencing metrics. Lineage density analyses demonstrate intra-tumoral heterogeneity with luminal subtype predominance across all samples. CD45+ cell analysis revealed significant heterogeneity of immune cell infiltrates (Figure 1). There were no significant differences in immune cell populations in HG vs. LG. Increased interferon gamma (IFNg) expression in tumor cells is associated with significantly increased immune cell infiltration (Spearman’s rank correlation r = 0.71, p=0.009). CONCLUSIONS: Our scRNA-seq data confirmed luminal subtype predominance and described the heterogeneous TME in UTUC. The statistically significant relationship of tumor cell IFNg with increased overall immune cell infiltration is notable and may have implications for systemic therapy response. Further high-resolution studies are needed to expand our knowledge of the molecular biology and TME of UTUC with implications for treatment selection and disease surveillance. Source of Funding: Thompson Family Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e863-e863 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter Reisz More articles by this author Andrew Tracey More articles by this author Fengshen Kuo More articles by this author Jasmine Thomas More articles by this author Quinlan Demac More articles by this author Tim Clinton More articles by this author Hong Truong More articles by this author Andrew Lenis More articles by this author Lucas Nogueira More articles by this author Karan Nagar More articles by this author Taha Merghoub More articles by this author Bernard Bochner More articles by this author Eugene Pietzak More articles by this author David Solit More articles by this author Kwanghee Kim More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement Loading ...