SPATIAL ANALYSIS OF THE TUMOR IMMUNE MICROENVIRONMENT IN PAPILLARY RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (PD16)1 May 2024PD16-01 SPATIAL ANALYSIS OF THE TUMOR IMMUNE MICROENVIRONMENT IN PAPILLARY RENAL CELL CARCINOMA Mitchell T. Hayes, Jose Laborde, Alex Soupir, Kirill Sabitov, Taylor Peak, Jonathan Nguyen, Carlos Moran-Segura, Daryoush Saeed-Vafa, Neale Lopez-Blanco, Paola Ramos Echevarria, Christopher Guske, Jodi Balasi, Jasremon Dhillon, Youngchul Kim, James Mule, Brooke L. Fridley, and Brandon J. Manley Mitchell T. HayesMitchell T. Hayes , Jose LabordeJose Laborde , Alex SoupirAlex Soupir , Kirill SabitovKirill Sabitov , Taylor PeakTaylor Peak , Jonathan NguyenJonathan Nguyen , Carlos Moran-SeguraCarlos Moran-Segura , Daryoush Saeed-VafaDaryoush Saeed-Vafa , Neale Lopez-BlancoNeale Lopez-Blanco , Paola Ramos EchevarriaPaola Ramos Echevarria , Christopher GuskeChristopher Guske , Jodi BalasiJodi Balasi , Jasremon DhillonJasremon Dhillon , Youngchul KimYoungchul Kim , James MuleJames Mule , Brooke L. FridleyBrooke L. Fridley , and Brandon J. ManleyBrandon J. Manley View All Author Informationhttps://doi.org/10.1097/01.JU.0001009560.23593.56.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Limited data exist on the tumor immune microenvironment (TIME) of papillary renal cell carcinoma (pRCC). We utilized multiplex immunofluorescence (mIF) and spatial transcriptomics using spatial molecular imaging (SMI) to evaluate spatial properties of the TIME in pRCC and contrasted these results with clear cell RCC (ccRCC). METHODS: Tumor specimens were obtained from localized RCC tumors. mIF was performed on regions of interest (ROI) selected from matched compartments from tumor, stroma, and tumoral/stromal subsets of the interface. Two antibody panels were used for markers against T cells and B cells/macrophages. Marker abundance and clustering differences were evaluated between pRCC and ccRCC, as well as between low and high clinical stages of pRCC (stage I/II vs III). The SMI platform used for validation utilized probes against 959 transcripts. Cell clustering was quantified using Ripley's K. Mixed linear models were used with random effects variables for ROI and patient. Statistical analyses were completed in R. RESULTS: mIF was performed on 1178 ROIs from 16 pRCC tumors and 70 ccRCC tumors. Compared to ccRCC, pRCC immune cell abundance was lower amongst many T cell types, largely driven by TBET+and FOXP3+ cells, and M2-like macrophages (CD163+ cells). Multiple macrophage marker positive cells exhibited higher clustering in pRCC, the most significant being CD68+CD163+ cells (p<0.001). Advanced clinical stage in pRCC was associated with higher abundance of CD3+CD8+ cells and lower clustering of CD68+PDL1+ cells (p<0.05). Higher abundance of CD68+CD163+ cells was associated with higher stage, but this was not statistically significant (p 0.095). Four ROIs from 2 pRCC patients underwent SMI validation. On SMI of the tumor compartment, T cells were clustered with other T cells, B cells, and M1 macrophages. CONCLUSIONS: Compared to ccRCC, pRCC has fewer T cells and macrophages; however pRCC had higher clustering of macrophages in the TIME. Higher abundance of CD8+ T cells is associated with worse clinical stage in localized pRCC. Using spatial transcriptomics, we found clustering between T cells, M1 macrophages, and B cells in pRCC. Source of Funding: Department of Defense US Army Medical Research Acquisition Activity Grant (KC180139), and a Moffitt Cancer Center Genitourinary Oncology Fellowship Research Grant (09-33494-22-01) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e365 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Mitchell T. Hayes More articles by this author Jose Laborde More articles by this author Alex Soupir More articles by this author Kirill Sabitov More articles by this author Taylor Peak More articles by this author Jonathan Nguyen More articles by this author Carlos Moran-Segura More articles by this author Daryoush Saeed-Vafa More articles by this author Neale Lopez-Blanco More articles by this author Paola Ramos Echevarria More articles by this author Christopher Guske More articles by this author Jodi Balasi More articles by this author Jasremon Dhillon More articles by this author Youngchul Kim More articles by this author James Mule More articles by this author Brooke L. Fridley More articles by this author Brandon J. Manley More articles by this author Expand All Advertisement PDF downloadLoading ...