Mp58-14 Using T Cell Receptor Sequencing to Characterize the Host Immune Response in Urothelial Carcinoma
Year: 2018
Type: article
Abstract: You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2018MP58-14 USING T CELL RECEPTOR SEQUENCING TO CHARACTERIZE THE HOST IMMUNE RESPONSE IN UROTHELIAL CARCINOMA Alexander Sankin, Damini Chand, Mark Schoenberg, and Xingxing Zang Alexander SankinAlexander Sankin More articles by this author , Damini ChandDamini Chand More articles by this author , Mark SchoenbergMark Schoenberg More articles by this author , and Xingxing ZangXingxing Zang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1846AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES High T cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer (Funt et al ASCO 2016). We hypothesized that T cell repertoire is more clonal in tumors than in benign inflammation. METHODS After obtaining IRB approval, we prospectively identified n=12 patients with bladder lesions at Montefiore Medical Center undergoing transurethral resection. Specimens were collected at time of transurethral resection and frozen and stored at -80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed. RESULTS There was an even distribution of specimens across all pathologic stages: 3/12 were T0, 3/12 were Ta, 3/12 were T1, and 3/12 were T2 or greater. The median number of productive TCR rearrangements sequenced in each sample in urothelial carcinoma specimens (UC+) and benign (UC-) specimens was 5,569 and 25,872 respectively. The median number of unique TCR rearrangements sequenced in UC+ and UC- specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte (TIL) percentage in UC+ and UC- specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T cell clone being present in up to 17% of the total TIL pool; in contrast, the frequency of the max T cell clone was 2% in UC- specimens (Figure 1). CONCLUSIONS Primary urothelial tumors contain clonally expanded T cell populations that are not present in benign urothelial inflammation. These data support the hypothesis that bladder tumors induce an antigen driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T cell clonal dominance. Future studies should be aimed to validate these results and to identify which tumor derived antigens are of clinical significance. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e778 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Alexander Sankin More articles by this author Damini Chand More articles by this author Mark Schoenberg More articles by this author Xingxing Zang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2796329358