MP61-14 SINGLE-CELL TRANSCRIPTOMICS REVEALS B CELLS-IgA-PIGR AIXS IMPROVING OVERALL SURVIVAL IN HPV-ASSOCIATED PENILE SQUAMOUS CELL CARCINOMAS

You have accessJournal of UrologyPenile & Testicular Cancer II (MP61)1 May 2024MP61-14 SINGLE-CELL TRANSCRIPTOMICS REVEALS B CELLS-IgA-PIGR AIXS IMPROVING OVERALL SURVIVAL IN HPV-ASSOCIATED PENILE SQUAMOUS CELL CARCINOMAS Tao Tao and Jun Xiao Tao TaoTao Tao and Jun XiaoJun Xiao View All Author Informationhttps://doi.org/10.1097/01.JU.0001009536.58867.87.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Human papillomavirus (HPV) is an oncogenic driver in up to 50% of patients with PSCC. While patients afflicted with HPV+ PSCCs have improved outcomes than HPV− PSCCs in clinic, the underlying mechanisms of these seemly controversial roles for HPV in PSCC remain unclear. METHODS: In this study, we collected the tumor and paracancerous tissues of HPV+ and HPV− PSCC patients. Through single-cell transcriptome sequencing and analysis to establish the PSCC single-cell map.Immunohistochemical staining was used to test the number of tertiary lymphoid structures (TLSs) and the expression level of PIGR, IgA, et al. ELISA assay was used to reveal the specific secretion of IgA in HPV+ tumor. Used BCR sequencing and single cell immunohistochemistry library sequencing technology to detected HPV+ tumor B cells' clonal proliferation diverse. The mouse tumor model was established by constructing the PIGR overexpression cell line. Finally, we analyzed the relationship between the survival prognosis of patients and PIGR and B cells in TCGA data. RESULTS: We applied single-cell RNA sequencing to describe the transcriptional profiles of 48,000 single cells from primary tumor or normal adjacent tissues (NATs) from treatment-naive HPV− and HPV+ PSCCs patients. The PSCC tumor tissues displayed a massive immune-cell infiltration compared to NATs. HPV+ PSCC tumor exhibited a significantly increased percentages of B cells, plasma cells, tertiary lymphoid structures (TLSs) and IgA secretion compared to HPV− PSCC tumor. We further identified a subset of HPV+ PSCC malignant epithelial cells expressing polymeric IgA receptor (PIGR), which mediates IgA transcytosis and elicits transcriptional changes that contributes to hindering malignant progression. PIGR overexpression in PSCC-derived primary cells or MC38 cell line inhibited tumor cell growth via B cells-IgA-PIGR signaling pathway. The high levels of IgA and PIGR in tumor tissues correlate with improved survival outcomes in PSCCs. CONCLUSIONS: Our work reveals previously unidentified markers and atlas of PSCCs, and demonstrate that the IgA-PIGR axis contributes to the clinical advantage in HPV+ PSCCs. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1016 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Tao Tao More articles by this author Jun Xiao More articles by this author Expand All Advertisement PDF downloadLoading ...