MP39-18 AN AUTOCHTHONOUS MOUSE MODEL OF KIDNEY CANCER WITH T CELL INFILTRATION

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-18 AN AUTOCHTHONOUS MOUSE MODEL OF KIDNEY CANCER WITH T CELL INFILTRATION Nitika Sharma, Bo Xu, Jacky Chow, Jason Muhitch, and Eric Kauffman Nitika SharmaNitika Sharma More articles by this author , Bo XuBo Xu More articles by this author , Jacky ChowJacky Chow More articles by this author , Jason MuhitchJason Muhitch More articles by this author , and Eric KauffmanEric Kauffman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immunocompetent animal models that recapitulate human renal cell carcinoma (RCC) and its tumor-immune microenvironment are critical for the preclinical study of novel immunotherapeutic strategies. Abundant CD8+ T cell lymphocyte infiltration is a defining feature of human clear cell RCC but is lacking from many mouse models. Iron is a known carcinogen with increased cellular levels in human RCC. In the FeNTA mouse model, chronic systemic administration of iron (Fe) with a chelator (nitrilotriacetic acid, NTA) induces renal carcinogenesis, however the tumor biology is largely uncharacterized. We studied whether FeNTA mouse model cancers have similar biology as human RCC, including an abundance of tumor-infiltrating lymphocytes. METHODS: 60 male mice (AJ strain) were treated for 12 weeks (5X/week) with intraperitoneal FeNTA injection to induce renal tumorigenesis. Renal tumors were harvested at 12-15 months post-treatment and underwent H&E histologic evaluation by a clinical genitourinary pathologist. Tumor lysates were analyzed for PAX8 and HIF2-alpha protein levels by Western Blot, while tumor single-cell suspensions were analyzed for immune cell antigens (CD45, CD3, CD4, CD8) by imaging flow cytometry to quantify tumor-infiltrating T cell lymphocyte populations. RESULTS: Of 60 FeNTA-treated mice, 14 (23.3%) developed renal tumors as confirmed by magnetic resonance imaging and histology. Mean tumor size was 1.5 cm (interquartile range 1.1-1.8 cm). Tumor histology was most similar to clinical clear cell RCC with eosinophilic cytoplasm. The clinical RCC biomarker, PAX8, was expressed in murine tumors, as was the HIF2-alpha protein that typifies human clear cell RCC. Infiltrating immune cells (CD45+) comprised on average 33.2% (+/- standard error, 4.6%) of all tumor cells, including 11.9% (+/- 3.9%) of tumor cells that were specifically T cell lymphocytes (CD45+/CD3+). Most tumor-infiltrating T cells were CD8+/CD4- (74.3+/- 3.7%), while the remainder were CD4+/CD8- (25.7+/- 3.7%). CONCLUSIONS: The FeNTA autochthonous immunocompetent mouse model recapitulates key clinical RCC biology, including a tumor-infiltrating T cell profile similar to that of the human disease. This model may provide a valuable resource for preclinical evaluation of novel immunotherapeutic strategies for RCC. Source of Funding: American Cancer Society © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e711-e712 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nitika Sharma More articles by this author Bo Xu More articles by this author Jacky Chow More articles by this author Jason Muhitch More articles by this author Eric Kauffman More articles by this author Expand All Advertisement Loading ...