294 EFFECT OF PAZOPANIB ON MYELOID DERIVED SUPPRESSOR CELLS AND T CELL FUNCTION IN METASTATIC RENAL CELL CARCINOMA PATIENTS

You have accessJournal of UrologyKidney Cancer: Basic Research (II)1 Apr 2013294 EFFECT OF PAZOPANIB ON MYELOID DERIVED SUPPRESSOR CELLS AND T CELL FUNCTION IN METASTATIC RENAL CELL CARCINOMA PATIENTS Kiranpreet Khurana, Pat Rayman, Paul Elson, Brian I. Rini, and James Finke Kiranpreet KhuranaKiranpreet Khurana Cleveland, OH More articles by this author , Pat RaymanPat Rayman Cleveland, OH More articles by this author , Paul ElsonPaul Elson Cleveland, OH More articles by this author , Brian I. RiniBrian I. Rini Cleveland, OH More articles by this author , and James FinkeJames Finke Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1678AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tyrosine kinase inhibitors have been shown to have an effect on T cell function. Sunitinib decreases immunosuppression in patients with metastatic renal cell carcinoma (mRCC) as seen by a reduction in myeloid derived suppressor cells (MDSC) that inhibit T cell function. The effect of pazopanib on immune function is unknown. METHODS Peripheral blood mononuclear cells (PBMCs) from patients with mRCC treated with pazopanib were obtained on cycle 1 day 1 (pre-treatment), cycle 1 day 28, cycle 2 day 28, and cycle 4 day 28 of 800 mg daily dosing adjusted for toxicity. Total MDSC and neutrophilic, monocytic, and lineage-negative MDSC subsets were measured by flow cytometry. T cell response was measured by interferon-gamma production after in vitro stimulation by anti-CD3/anti-CD28 beads. Pre-treatment levels were compared to cycle 4 day 28. RESULTS In this cohort of 21 mRCC patients, MDSCs comprised 4.7 % (median; range 1.7-32.9 %) of the PBMCs pre-treatment. The neutrophilic MDSC subset was the most prevalent at 2.0 % (median; range 0.3-30.4 %) followed by monocytic MDSC (median 1.5 %; range 0.4-5.3 %), and lineage-negative MDSC subset (median 0.15%; range 0.01-1.03 %). Pazopanib did not significantly decrease the percentage of MDSC (total or subpopulations) over time with the possible exception of a modest decrease in the lineage-negative MDSC subset (p=0.08). In contrast, treatment with pazopanib was associated with a significant increase over time in CD3+ interferon-gamma levels (median 37% increase; range -85%-605%, p=.03). CONCLUSIONS Pazopanib did not significantly impact MDSC levels in patients with mRCC. It was, however, associated with improved T cell function over time, as seen by a significant increase in CD3+ interferon-gamma production. Further studies are investigating possible mechanisms of action of these findings with the goal of combining synergistic immunomodulatory therapy with pazopanib to enhance anti-tumoral response in metastatic renal cell carcinoma. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e119-e120 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Kiranpreet Khurana Cleveland, OH More articles by this author Pat Rayman Cleveland, OH More articles by this author Paul Elson Cleveland, OH More articles by this author Brian I. Rini Cleveland, OH More articles by this author James Finke Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...