365 ANALYSIS OF REGULATORY T CELLS IN PATIENTS AFFECTED BY RENAL CELL CARCINOMA (2010)

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2010365 ANALYSIS OF REGULATORY T CELLS IN PATIENTS AFFECTED BY RENAL CELL CARCINOMA Paolo Traverso, Gilberto Filaci, Virginia Varca, Daniela Fenoglio, Aldo Franco De Rose, and Giorgio Carmignani Paolo TraversoPaolo Traverso More articles by this author , Gilberto FilaciGilberto Filaci More articles by this author , Virginia VarcaVirginia Varca More articles by this author , Daniela FenoglioDaniela Fenoglio More articles by this author , Aldo Franco De RoseAldo Franco De Rose More articles by this author , and Giorgio CarmignaniGiorgio Carmignani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.432AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Regulatory T lymphocytes (T-reg) are required for maintaining immune homeostasis since they control the activity of effector and/or autoreactive T cells. However, in cancer their function could be deleterious for patients because it can inhibit anti-cancer immune responses.Therefore it is of importance to evaluate T-reg activity in cancer patients to understand whether they are functional and enriched in the tumor microenvironment. This could have pathogenic and prognostic relevance in renal cell carcinoma which is therapeutically an orphan disease with the exception of surgical treatment. Objectives: to analyse number and function of CD4+CD25+ and CD8+CD28- T-reg subpopulations in the peripheral blood, loco-regional lymph nodes and tumor specimens from 10 patients with renal cell carcinoma. METHODS Ten consecutive patients underwent radical nephrectomy for renal tumor. Intraoperative bleeding and surgical specimens were processed in order to purify the mononuclear cells by centrifugation on Ficoll gradient. Purified subpopulations were achieved by magnetic bead cell sorting using beads conjugated with specific monoclonal antibodies. Cell frequency and function were evaluated using fluorescence-activated cell sorter (FACS) and suppression assays. RESULTS Increased frequencies of both CD4+C25+ and CD8+CD28- were detected in the peripheral blood. Interestingly, CD8+CD28- expressed significantly higher levels of CD39 and GITR antigens with respect to healthy controls. Of note, functional CD8+CD28- T-reg were observed in the circulation, a finding never occurring in healthy subjects. Significant (>30%) suppressor activity was exerted by intratumoral lymphocytes (TILs) purified from 8 out of 10 patients. Intratumoral CD8+CD28- T lymphocytes showed elevated expression of CD39 antigen in 6 out of 10 patients. Relevant CD8+CD28- T cell mediated suppressor activity was detected in the only metastatic hilar lymph node. CONCLUSIONS Both CD4+CD25+ and CD8+CD28- T-reg subpopulations have been identified in the peripheral blood and tumor specimens of patients. These cells are highly enriched and functional, suggesting a role in inducing tumor escape from immune system control. In some patients the function activity of T-reg correlated with elevated expression of CD39 and GITR antigens, which may be involved in the regulatory function. Data underline the possible role of both T-reg subpopulations in tumor pathogenesis and prognosis. Furthermore, they suggest the importance of counteracting regulatory responses in the setting of renal cancer specific immunotherapies. Genoa, Italy© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e144-e145 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paolo Traverso More articles by this author Gilberto Filaci More articles by this author Virginia Varca More articles by this author Daniela Fenoglio More articles by this author Aldo Franco De Rose More articles by this author Giorgio Carmignani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...