MP04-19 IMPACT OF SURGERY ON CYTOTOXIC ACTIVITY OF PATIENT-DRIVEN CD8 T CELL

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP04-19 IMPACT OF SURGERY ON CYTOTOXIC ACTIVITY OF PATIENT-DRIVEN CD8 T CELL Reza Nabavizadeh, Rodrigo Rodrigues Pessoa, Zesheng An, Joanina Gicobi, Susan Harrington, Henan Zhang, Tianxiao Xu, Jacob Hirdler, Christine Lohse, Bradley Leibovich, Haidong Dong, and Fabrice Lucien Reza NabavizadehReza Nabavizadeh More articles by this author , Rodrigo Rodrigues PessoaRodrigo Rodrigues Pessoa More articles by this author , Zesheng AnZesheng An More articles by this author , Joanina GicobiJoanina Gicobi More articles by this author , Susan HarringtonSusan Harrington More articles by this author , Henan ZhangHenan Zhang More articles by this author , Tianxiao XuTianxiao Xu More articles by this author , Jacob HirdlerJacob Hirdler More articles by this author , Christine LohseChristine Lohse More articles by this author , Bradley LeibovichBradley Leibovich More articles by this author , Haidong DongHaidong Dong More articles by this author , and Fabrice LucienFabrice Lucien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal cell carcinoma (RCC) elicits immune dysfunction through infiltration of immunosuppressive cells and expression of immuno-inhibitory molecules such as PD-L1. The impact of removing primary malignancy on boosting systemic antitumor immunity remains unclear. Here, we investigated the impact of nephrectomy on cytotoxic activity of patient-driven CD8 T cells. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 11 prospectively enrolled patients before and at 3-month post nephrectomy for clear cell RCC. Human 786-O ccRCC cells was used as target cells and killing rates were measured by calcein release assay. Wilcoxon paired t test and Mann Whitney test were used for analysis. RESULTS: Five patients showed detectable patient-derived CD8 T cells killing at baseline and this number increased to 7 at 3 months. Four patients showed no T-cell killing at both baseline and 3 months. The killing rate was 1.9 higher at 3-month compared to baseline, 21.4% (range 0%-52.5%) versus 11.4% (range 4.0% to 32.5%), respectively (p=0.0245). Level of tumor-reactive CD11ahighCD8 T cells at 3 months was increased in 7 patients compared to baseline while 2 patients showed decreased and another 2 had unchanged levels. For T cells positive for CX3CR1 and GZMB, 6 patients showed increased levels at 3 months, 2 decreased and 3 had unchanged levels. At 3 months, patients that had T cell cytotoxic activity had higher levels of CD11a (mean 10.27% vs 7.7%, p=0.20) and CX3CR1 and GZMB (mean 9.62% vs 19.6%, p=0.11), two marker of enhanced cytotoxicity. There were lower levels of tumor-reactive effector CD8 T cells in patients with blood concentrations of PD-L1>1 ng/ml compared to patients with ≤1 ng/ml (mean 6.146 ng/ml vs 0.121 ng/ml; p=0.032) (Figure 1). CONCLUSIONS: Nephrectomy is associated with an increase rate and enhanced tumor cell killing ability of peripheral CD8 T cells. Higher levels of CD11a, CX3CR1 and GZMB CD8 T cells as well as lower PD-L1 serum levels after surgery were associated with higher cytotoxic activity of patient-derived tumor-reactive effector CD8 T cells. Source of Funding: This work was supported by NIH R01CA256927 and R01AI095239 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e41 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Reza Nabavizadeh More articles by this author Rodrigo Rodrigues Pessoa More articles by this author Zesheng An More articles by this author Joanina Gicobi More articles by this author Susan Harrington More articles by this author Henan Zhang More articles by this author Tianxiao Xu More articles by this author Jacob Hirdler More articles by this author Christine Lohse More articles by this author Bradley Leibovich More articles by this author Haidong Dong More articles by this author Fabrice Lucien More articles by this author Expand All Advertisement PDF downloadLoading ...